Patents.us
Patents/US11725045

Anti-respiratory Syncytial Virus Antibodies, Methods of Their Generation and Use

US11725045No. 11,725,045utilityGranted 8/15/2023

Abstract

Provided are antibodies or antigen binding polypeptides characterized by the ability to neutralize respiratory syncytial virus (RSV). Specifically, the antibodies or antigen binding polypeptides are characterized by high affinity binding to RSV fusion glycoprotein (RSVF). Further provided are methods for their identification, isolation, generation, preparation, and use, as well as the heavy chain and light chain sequences of the antibodies provided.

Claims (45)

Claim 1 (Independent)

1. A composition comprising an antibody component, wherein: the antibody component consists of: a first antibody, or antigen binding fragment thereof, that has heavy and light chain CDRs found in antibody number 843; and a second antibody, or antigen binding fragment thereof, that has heavy and light chain CDRs found in an antibody that is selected from the group consisting of antibody numbers 554, 466, 2, 71, 112, 217, 227, 228, 249, 467, 469, 470, 832, 471, 516, 527, 532, 543, 544, 551, 571, 578, 581, 592, 615, 641, 868, and 870; wherein each of the first and second antibodies, or antigen binding fragments thereof, specifically binds to and neutralizes RSV F; and further wherein the composition does not include any antibodies other than the antibody component.

Show 44 dependent claims
Claim 2 (depends on 1)

2. The composition of claim 1 , wherein either the first and/or second antibody has an IC50 of less than 300 pM for neutralization of RSV.

Claim 3 (depends on 1)

3. The composition of claim 1 , wherein either the first and/or second antibody has an IC50 of less than 200 pM for neutralization of RSV.

Claim 4 (depends on 1)

4. The composition of claim 1 , wherein either the first and/or second antibody has an IC50 of less than 100 pM for neutralization of RSV.

Claim 5 (depends on 1)

5. The composition of claim 1 , wherein each of the first and second antibody is characterized by binding affinity to pre-F with a k D of less than 10 nM.

Claim 6 (depends on 1)

6. A method of treating an RSV infection in a mammal, comprising administering the composition of claim 1 .

Claim 7 (depends on 6)

7. The method according to claim 6 , wherein the method further comprises administering to the mammal an additional prophylactic or therapeutic agent.

Claim 8 (depends on 7)

8. The method according to claim 7 , wherein the additional prophylactic or therapeutic agent is one or more of: an antiviral agent; a vaccine specific for RSV; a vaccine specific for influenza virus; a vaccine specific for metapneumovirus (MPV); an siRNA specific for a RSV antigen; an siRNA specific for a MPV antigen; a further anti-RSV antibody; an anti-MPV antibody; an anti-IL4R antibody; an anti-influenza antibody; and a NSAID.

Claim 9 (depends on 6)

9. The method according to claim 6 , wherein the mammal is a human.

Claim 10 (depends on 1)

10. The composition of claim 1 , wherein the first antibody has framework regions with at least 90% sequence identity to those of antibody number 843, and/or the second antibody has framework regions with at least 90% sequence identity to the framework regions of the antibody in which its heavy and light chain CDRs are found.

Claim 11 (depends on 1)

11. The composition of claim 1 , wherein the first antibody and/or second antibody comprise a heavy chain IgG Fc region.

Claim 12 (depends on 11)

12. The composition of claim 11 , wherein the heavy chain IgG Fc region is a variant associated with increased antibody serum half-life, improved stability, modified effector function, or a combination thereof.

Claim 13 (depends on 1)

13. The composition of claim 1 , which composition consists of: the antibody component; and a carrier for parenteral administration.

Claim 14 (depends on 1)

14. The composition of claim 1 , which composition is formulated for parenteral administration.

Claim 15 (depends on 13)

15. The composition of claim 13 , which composition is in powder form.

Claim 16 (depends on 1)

16. The composition of claim 1 , which composition is formulated for intravenous-, intramuscular-, intradermal-, transdermal-, intraperitoneal, intranasal-, inhalation, and/or subcutaneous-administration and/or intramuscular administration.

Claim 17 (depends on 14)

17. The composition of claim 14 , disposed within a syringe.

Claim 18 (depends on 1)

18. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 554.

Claim 19 (depends on 1)

19. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 466.

Claim 20 (depends on 1)

20. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 2.

Claim 21 (depends on 1)

21. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 71.

Claim 22 (depends on 1)

22. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 112.

Claim 23 (depends on 1)

23. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 217.

Claim 24 (depends on 1)

24. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 227.

Claim 25 (depends on 1)

25. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 228.

Claim 26 (depends on 1)

26. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 249.

Claim 27 (depends on 1)

27. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 467.

Claim 28 (depends on 1)

28. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 469.

Claim 29 (depends on 1)

29. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 470.

Claim 30 (depends on 1)

30. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 832.

Claim 31 (depends on 1)

31. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 471.

Claim 32 (depends on 1)

32. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 516.

Claim 33 (depends on 1)

33. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 527.

Claim 34 (depends on 1)

34. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 532.

Claim 35 (depends on 1)

35. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 543.

Claim 36 (depends on 1)

36. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 544.

Claim 37 (depends on 1)

37. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 551.

Claim 38 (depends on 1)

38. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 571.

Claim 39 (depends on 1)

39. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 578.

Claim 40 (depends on 1)

40. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 581.

Claim 41 (depends on 1)

41. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 592.

Claim 42 (depends on 1)

42. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 615.

Claim 43 (depends on 1)

43. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 641.

Claim 44 (depends on 1)

44. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 868.

Claim 45 (depends on 1)

45. The composition of claim 1 , wherein the second antibody, or antigen binding fragment thereof, has heavy and light chain CDRs found in antibody number 870.

Full Description

Show full text →

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a national stage filing under 35 U.S.C. § 371 of International PCT Application No. PCT/US2018/055750 filed Oct. 12, 2018, which claims the benefit of U.S. Provisional Application No. 62/572,400 filed Oct. 13, 2017, the contents of all of which are herein incorporated by reference in their entirety.

SEQUENCE LISTING

This application contains a Sequence Listing filed herewith in ASCII format named 2009186_0296_SL.txt, created on Aug. 18, 2021 and 2,383,864 bytes in size. The Sequence Listing is incorporated by reference herein.

FIELD OF THE INVENTION

The invention is related to human antibodies and antigen-binding fragments thereof that specifically bind to Respiratory Syncytial Virus fusion glycoprotein (RSV F) (“anti-RSV F antibodies”), in particular infant anti-RSV F antibodies, compositions comprising these antibodies, and methods for the preparation and use of these antibodies.

BACKGROUND OF THE INVENTION

Respiratory syncytial virus (RSV) is a ubiquitous pathogen that causes bronchiolitis and pneumonia in infants and the elderly and substantial morbidity and mortality in infants, the elderly, and immunocompromised individuals. Recent estimates indicate that RSV causes nearly 60,000 deaths annually in children under the age of five (Shi et al., 2017). Currently, the only preventive measure available for RSV is passive prophylaxis with the monoclonal antibody Synagis® (Group, 1998). Unfortunately, prophylaxis with Synagis® is costly, requires multiple doses per RSV season, and is only modestly efficacious (Group, 1998; Homaira et al., 2014; Kamal-Bahl et al., 2002). These factors restrict its use to high-risk infants and limit its availability in developing countries where the greatest burden of RSV-associated mortality exists. Therefore, the development of an effective RSV vaccine and next-generation monoclonal antibodies is of great importance and ongoing clinical trials are evaluating numerous candidates (Griffin et al., 2017; PATH, 2017; Reichert, 2016; Zhu et al., 2017).

The development of an RSV vaccine has proven to be particularly challenging, due in part to the young age at which primary infection occurs (Glezen et al., 1986), a history of vaccine-enhanced disease in infants (Chin et al., 1969; Fulginiti et al., 1969; Kapikian et al., 1969; Kim et al., 1969), and a lack of long-lived immunity in response to natural infection, resulting in frequent reinfections (Hall et al., 1991; Henderson et al., 1979). Although there are no clinically approved RSV vaccines, there are 43 vaccine candidates in development, of which 19 are in clinical stage development (Center for Vaccine Innovation and Access, PATH available on the world wide web at path.org/programs/center-for-vaccine-innovation-and-access/). Most of these vaccines seek to induce neutralizing antibodies that recognize the RSV fusion (F) glycoprotein, which is targeted by the prophylactic antibody palivizumab and the majority of RSV-specific neutralizing antibodies in human sera.

The goal of most vaccination efforts against RSV is not to prevent infection, but to reduce the risk of RSV-related complications in high-risk populations, such as infants and the elderly. Five target age groups for vaccination have been proposed—infants under six months of age, infants over six months of age, school-aged children, pregnant women, and adults over 65 years old—with the goal of either directly or indirectly protecting at-risk populations (Anderson et al., 2013). These target age groups have different immunological characteristics that may require different vaccination strategies for optimal protection. Although multiple modalities for an RSV vaccine are currently being pursued, most vaccination strategies share a common goal: to elicit neutralizing antibodies that recognize the RSV fusion glycoprotein (RSV F), which is targeted by the majority of RSV-neutralizing activity in human sera (Magro et al., 2012; Sastre et al., 2005).

RSV F is a class I fusion protein that mediates viral entry into host cells by converting from a metastable prefusion conformation (preF) to a highly stable postfusion (postF) conformation. On the surface of the virus, RSV F exists in a metastable trimeric prefusion conformation (preF) before undergoing a dramatic structural rearrangement that results in the insertion of a hydrophobic fusion peptide into the host-cell membrane. This intermediate state of RSV F tethers the viral and host-cell membranes before collapsing to form the stable six-helix bundle that is characteristic of the postfusion conformation (postF). Fusion of the viral and host-cell membranes is driven by these conformational changes, and the antigenic topology of RSV F is substantially altered during this transition. Over the past several years, epitope mapping studies using both human and murine monoclonal antibodies have defined at least 6 major antigenic sites on the RSV F protein. Some groups of epitopes, referred to as antigenic sites, are generally conserved on both the preF and postF, whereas others antigenic sites are preferentially or exclusively expressed on only one conformation (Graham, 2017; McLellan et al., 2013; McLellan et al., 2011; Swanson et al., 2011). Molecules that prevent these structural changes can prevent viral fusion and have potential as therapeutics for RSV (Battles et al., 2016; Huang et al., 2010; Lambert et al., 1996; McLellan et al., 2013). Recent studies have shown that the vast majority of highly potent neutralizing antibodies target epitopes that are exclusively expressed on preF. Hence, vaccines that specifically induce preF-specific antibodies may have great clinical potential.

The first characterized RSV F-reactive antibodies bound to structural elements shared by both preF and postF and were F-conformation-independent. These include Synagis®, which recognizes a helix-turn-helix motif called antigenic site II (Beeler and van Wyke Coelingh, 1989; McLellan et al., 2010b), and 101F, which recognizes the β-strand-rich antigenic site IV (McLellan et al., 2010a; Wu et al., 2007). Antibodies that preferentially bind to postF at antigenic site I were also among the first to be isolated, but were only weakly neutralizing (Anderson et al., 1986; Garcia-Barreno et al., 1989). The first preF-specific antibodies to be described recognized antigenic site Ø, present at the apex of the preF trimer, and were shown to be extremely potent (McLellan et al., 2013). A second class of potently neutralizing antibodies, epitomized by MPE8, was later described and shown to recognize antigenic site III (Corti et al., 2013). Although the secondary structure elements that form site III are present on both preF and postF, they adopt a different spatial arrangement in postF that dramatically decreases the affinity of site III-directed antibodies for this conformation and results in preferential binding to preF (Corti et al., 2013; Rossey et al., 2017; Wen et al., 2017). Antigenic site V, located between sites Ø and III, was recently identified and shown to be the target of additional preF-specific antibodies that are also potently neutralizing (Gilman et al., 2016; Mousa et al., 2017). The isolation and characterization of preF-specific antibodies spurred the development of second-generation prophylactics, such as MEDI8897, which recognizes site Ø (Griffin et al., 2017; Zhu et al., 2017) and is currently in late-phase clinical trials as a potential replacement for Synagis®.

An effective RSV vaccine will likely require the elicitation of potent neutralizing antibodies and balanced cellular responses (Kristjansson et al., 2005; Lambert et al., 2014; Legg et al., 2003; Saravia et al., 2015; Zhang et al., 2017). Infants present a number of unique challenges for vaccine development, including suppression of B cell responses by maternally derived antibody (Gans et al., 2001; Sande et al., 2014; Trang et al., 2014; Troisi et al., 1997; Wang et al., 2017) and immunological immaturity that results in reduced levels of T cell help, antibody class-switching, and somatic hypermutation (SHM) (Siegrist and Aspinall, 2009). Studies of convalescent infant sera have demonstrated that infants generally produce low titers of RSV-neutralizing antibodies after natural infection (Esposito et al., 2016; Murphy et al., 1986; Sande et al., 2014) but that these titers are higher when levels of maternal antibody are low (Shinoff et al., 2008), suggesting that infants are capable of mounting neutralizing antibody responses to RSV under certain circumstances. Serum studies have also suggested that different epitopes may be targeted as children age into adulthood (Fuentes et al., 2016), but little is known about how these changes are associated with antibody sequence or neutralization potency. In addition, sequencing studies have demonstrated that the antibody variable genes cloned from RSV-specific B cells in infants under three months of age contain little to no SHM, but the corresponding antibodies were not produced and characterized (Williams et al., 2009).

RSV replicates exclusively in respiratory epithelial cells, initiating infection in the upper respiratory tract and in some cases progressing to the lower respiratory tract. Therefore, an effective RSV vaccine may induce systemic and mucosal immune responses that protect both the upper and lower respiratory tracts (Varga, Current Opinion in Virology, 2014). A substantial body of literature suggests that RSV-specific mucosal antibody levels correlate more strongly with protection against RSV infection than serum antibody titers (Mills J T J Immnology 1971; Singleton R et al, JVI, 2003; walsh EE et al, JID, 2004; Habibi, AJRCCM 2015; Bagga JID, 2015; Vissers, CVI 2016; Watt P J Vaccine 1990). For example, experimental RSV challenge studies in adult donors have shown that nasal antibody strongly predicts protection from RSV infection (Habibi, AJRCCM 2015). In addition, a recent study in a clinical pediatric cohort showed that high levels of RSV-specific mucosal IgG correlated with reduced viral load and inflammation, whereas plasma IgG levels were not predictive of either (Vissers, CVI 2016). Finally, preclinical immunogenicity and efficacy studies utilizing a live-attenuated vaccine candidate, RGΔM2-2, showed that the protective efficacy of this vaccine was significantly higher when delivered by the intrasanal route compared to the intramuscular route, despite both vaccines inducing comparable serum antibody titers. These studies provide compelling evidence that mucosal immunity may be required for efficient protection against RSV. However, relatively little is known about the anatomic location(s) of RSV-specific memory B cells within mucosa-associated lymphoid tissues, the specificities and functional properties of these antibodies, and if/how the RSV-specific mucosal antibody response differs from the systemic antibody response. A better understanding of these aspects of RSV infection and immune responses may provide useful information for the development of effective RSV vaccines.

SUMMARY OF THE INVENTION

An improved understanding of the specificities and functional activities of antibodies induced by natural RSV infection in young infants could facilitate the design of vaccine antigens that are less susceptible to interference by maternal antibodies and that focus the response on epitopes associated with neutralizing activity. RSV is a leading cause of infant mortality, and there are currently no licensed vaccines to protect this vulnerable population. A comprehensive understanding of infant antibody responses to natural RSV infection will facilitate vaccine development.

Applicant has discovered, isolated, and characterized an extensive panel of RSV F-specific monoclonal antibodies from several RSV-infected infants, some of which antibodies recognize antigenic sites distinct from those sites that dominate adult responses. In particular, over 450 RSV F-specific antibodies from the peripheral B cells of seven RSV-infected infants were isolated and characterized and, additionally, over 800 RSV F-specific antibodies from paired peripheral blood and adenoid tissues of 6 young children were isolated and characterized.

Binding and functional studies of the isolated anti-RSV F infant antibodies generally demonstrate binding to 2 primary antigenic sites and different neutralization potentials, i.e., non-neutralizing antibodies that bind to site I on postfusion F and neutralizing antibodies that bind to site III or site V on postfusion F. Structural studies provide a molecular basis for the conserved features of antibodies recognizing these sites. A subset of antibodies targeting one of the sites displayed potent neutralizing activity despite lacking somatic mutations, suggesting such antibodies can be induced in young infants with suitably designed vaccine antigens. Accordingly, Applicant provides fundamental insights into infant antibody responses in different immune compartments (e.g., mucosal and systemic) and, thus, provides a blueprint for the rational design of infant vaccine immunogens that selectively elicit desired B cell responses in infants.

In some embodiments, the present disclosure provides isolated antibodies or antigen-binding polypeptides comprising a VH CDR3 having an amino acid sequence according to an antibody number in Table 9B.

In some embodiments, the present disclosure provides isolated antibodies or antigen-binding polypeptides comprising a VH CDR3 having an amino acid sequence according to an ADI listed in Table 8.

In some embodiments, the present disclosure provides isolated antibodies or antigen binding polypeptides characterized by ability to neutralize respiratory syncytial virus (RSV).

In some embodiments, antibodies or antigen binding polypeptides are characterized by high affinity binding to RSV F.

In some embodiments, antibodies or antigen binding polypeptides are characterized by high affinity binding to RSV prefusion F (preF).

In some embodiments, isolated antibodies have an amino acid sequence according to:

(i) Antibody Number 2, 71, 112, 217, 227, 228, 249, 466, 467, 469, 470, 832, 471, 516, 527, 532, 543, 544, 551, 554, 571, 578, 581, 592, 615, 641, 843, 868, or 870;

(ii) an Antibody Number of (i) with no more than 3 amino acid substitutions, additions, or deletions;

(iii) an Antibody Number of (i) with no more than 3, 2, or 1 amino acid substitution(s), addition(s), or deletion(s) in a CDR; or

(iv) an Antibody Number of (i) with no more than 3, 2, or 1 amino acid substitution(s), addition(s), or deletion(s) in CDRH3.

In some embodiments, antibodies or antigen-binding polypeptides have an IC50 of less than 300 pM, less than 200 pM, or less than 100 pM for neutralization of RSV.

In some embodiments, antibodies or antigen-binding polypeptides are characterized by binding affinity to pre-F with a kD of less than 10 nM.

In some embodiments, antibodies or antigen-binding polypeptides characterized by a binding affinity to pre-F that is at least 10, 100, or 1000 fold greater than binding affinity to post-F.

In some embodiments, antibodies or antigen-binding polypeptides are characterized by high affinity binding to RSV F site III.

In some embodiments, the present disclosure provides an antibody or antigen-binding fragment thereof that cross-competes for binding or specifically binds to the same epitope(s) of a Respiratory Syncytial Virus (RSV) fusion glycoprotein (F) (“an anti-RSV F antibody”) as an antibody or antigen-binding fragment thereof comprising a CDRH3 amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a CDRH3 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

The present disclosure also provides an antibody or antigen-binding fragment thereof that cross-competes for binding or specifically binds to the same epitope(s) of a Respiratory Syncytial Virus (RSV) fusion glycoprotein (F) (“an anti-RSV F antibody”) as an antibody or antigen-binding fragment thereof comprising a CDRH2 amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a CDRH2 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

The present disclosure further provides an antibody or antigen-binding fragment thereof that cross-competes for binding or specifically binds to the same epitope(s) of a Respiratory Syncytial Virus (RSV) fusion glycoprotein (F) (“an anti-RSV F antibody”) as an antibody or antigen-binding fragment thereof comprising a CDRH1 amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a CDRH1 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

The present disclosure also provides an antibody or antigen-binding fragment thereof that cross-competes for binding or specifically binds to the same epitope(s) of a Respiratory Syncytial Virus (RSV) fusion glycoprotein (F) (“an anti-RSV F antibody”) as an antibody or antigen-binding fragment thereof comprising a CDRL3 amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a CDRL3 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

The present disclosure further provides an antibody or antigen-binding fragment thereof that cross-competes for binding or specifically binds to the same epitope(s) of a Respiratory Syncytial Virus (RSV) fusion glycoprotein (F) (“an anti-RSV F antibody”) as an antibody or antigen-binding fragment thereof comprising a CDRL2 amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a CDRL2 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

The present disclosure also provides an antibody or antigen-binding fragment thereof that cross-competes for binding or specifically binds to the same epitope(s) of a Respiratory Syncytial Virus (RSV) fusion glycoprotein (F) (“an anti-RSV F antibody”) as an antibody or antigen-binding fragment thereof comprising a CDRL1 amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a CDRL1 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

In some embodiments, the anti-RSV F antibody comprises (i) the CDRH3 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5; (ii) the CDRH2 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5; (iii) the CDRH1 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5; (iv) the CDRL3 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5; (v) the CDRL2 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5; (vi) the CDRL1 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5; or (vii) any combination of two or more of (i), (ii), (iii), (iv), (v), and (vi).

In other embodiments, the antibody or antigen-binding fragment thereof that cross-competes for binding or specifically binds to the same epitope(s) of a Respiratory Syncytial Virus (RSV) fusion glycoprotein (F) (“an anti-RSV F antibody”) as an antibody or antigen-binding fragment thereof comprising (i) a heavy chain variable region (VH) that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a V H amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5, and/or (ii) a light chain variable region (V L ) that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a V L amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

In yet other embodiments, the anti-RSV F antibody comprises (i) the V H amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5; and/or (ii) the V L amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

In certain embodiments, the anti-RSV F antibody is selected from the group consisting of Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

In some embodiments, the anti-RSV F antibody binds to an epitope comprising site Ø, site I, site II, site III, site IV, or site V of RSV F. In one embodiment, the anti-RSV F antibody binds to an epitope on prefusion F (preF), preferably antigenic site III. In other embodiments, the anti-RSV F antibody binds to an epitope on postfusion F (post F), preferably antigenic site I.

In some embodiments, the anti-RSV F antibody binds to prefusion F (preF) with high affinity but does not bind to or binds with low affinity to postfusion F (postF).

In some embodiments, the anti-RSV F antibody does not compete with D25 for binding to RSV F. In some embodiments, the anti-RSV F antibody competes with MPE8 and/or motavizumab for binding to RSV F.

In some embodiments, the anti-RSV F antibody is a neutralizing antibody. In a certain embodiment, the anti-RSV F antibody has a neutralizing activity (IC 50 ) of less than 100 μg/ml, 50 μg/ml, 25 μg/ml, 10 μg/ml, 5 μg/ml, 1 μg/ml, 0.5 μg/ml, 0.1 μg/ml, or 0.05 μg/ml.

In some embodiments, the anti-RSV F antibody binds to RSV prefusion F with a K D value of less than 50 nM, 25 nM, 10 nM, 5 nM, 1 nM, 0.5 nM, or 0.1 nM as measured by surface plasmon resonance.

In some embodiments, the anti-RSV F antibody binds to RSV prefusion F through one or both of the following interactions: a) Tyr33 in CDRL1 and Tyr93 in CDRL3 both contact the α6-α7 loop of RSV prefusion F; and b) five consecutive serine residues, preferably followed by a tyrosine residue (Tyr56), in CDRH2 form a network of hydrogen bonds with Asp310 on β6 of RSV prefusion F.

In some embodiments, the anti-RSV F antibody has a clean or low polyreactivity profile.

In some embodiments, the anti-RSV F antibody is a full-length IgG1 monoclonal antibody.

In some embodiments, the anti-RSV F antibody is a human antibody.

In some embodiments, the anti-RSV F antibody comprises a Fc region that has been modified to alter effector function, half-life, proteolysis, and/or glycosylation.

In some embodiments, the anti-RSV F antibody is derivatized.

The present disclosure further encompasses a nucleic acid sequence or nucleic acid sequences encoding the anti-RSV F antibodies described herein; expression vectors comprising the isolated nucleic acid sequence(s); and host cell(s) comprising the isolated nucleic acid sequence(s) or the expression vector(s). In some embodiments, the host cell is a mammalian cell, a bacterial cell, a fungal cell, a yeast cell, or an insect cell.

Additionally, the present disclosure encompasses a method for producing an isolated human antibody or antigen-binding fragment thereof that specifically binds to Respiratory Syncytial Virus (RSV) fusion glycoprotein (F) (“an anti-RSV F antibody”) comprising expressing the nucleic acid sequence(s) described herein or culturing the host cell(s) described herein (e.g., a yeast cell or a mammalian cell) under conditions that provide for expression of the anti-RSV F antibody and optionally recovering the anti-RSV F antibody from the host cell and/or culture medium.

The present disclosure also contemplates a pharmaceutical composition comprising (i) an anti-RSV F antibody(ies) described herein, the nucleic acid sequence(s) described herein, the expression vector(s) described herein, or the host cell(s) described herein; and (ii) a pharmaceutically acceptable carrier and/or excipient. The pharmaceutical composition can be used for preventing or treating a RSV infection in a subject. In one embodiment, the subject is a human, preferably an infant.

Furthermore, the present disclosure encompasses a method of preventing or treating a Respiratory Syncytial Virus (RSV) infection in a subject (e.g., a human or a non-human), comprising administering to the subject in need thereof an effective amount of the anti-RSV F antibody(ies) described herein, the isolated nucleic acid sequence(s) described herein, the expression vector(s) described herein, or the host cell(s) described herein, optionally in association with a further prophylactic and/or therapeutic agent. In one embodiment, the further prophylactic and/or therapeutic agent is selected from an antiviral agent; a vaccine specific for RSV; a vaccine specific for influenza virus; a vaccine specific for metapneumovirus (MPV); an siRNA specific for a RSV antigen; an siRNA specific for a MPV antigen; a second anti-RSV antibody; an anti-MPV antibody; an anti-IL4R antibody; an anti-influenza antibody; and a NSAID. In some embodiments, the subject is a human, preferably an infant.

Also provided herein is a method of preventing or treating a Respiratory Syncytial Virus (RSV) infection in a human subject (e.g., an infant) comprising administering to the subject in need thereof an effective amount of the pharmaceutical composition described herein.

Additionally provided herein is a method for detecting a Respiratory Syncytial Virus (RSV) infection in a subject (e.g., a human or a non-human) comprising obtaining a sample from the subject; contacting the sample with the anti-RSV F antibody(ies) described herein; and detecting the presence of a complex between the anti-RSV F antibody and the RSV fusion glycoprotein (F), wherein detection of the complex indicates the presence of RSV. In one embodiment, the subject is a human subject, preferably an infant.

Other features and advantages of the instant invention will be apparent from the following detailed description and examples which should not be construed as limiting. The contents of all cited references, including scientific articles, patents and patent applications cited throughout this application, are expressly incorporated herein by reference.

BRIEF DESCRIPTION OF THE FIGURES

FIGS. 1 A- 1 C show the single B cell sorting strategy. FIG. 1 A shows the gating strategy for a representative infant ≥6 months (Infant 2042), and FIG. 1 B shows the gating strategy for a representative infant <3 months (Infant 2026). Lymphocytes were gated based on forward and side scatter, followed by a live/dead gate and selection of CD3 − CD8 − CD 14 − cells. B cells were identified by gating on CD19 + /CD20 + cells. IgG + or IgA + B cells or CD19/CD20 + B cells that showed reactivity with RSV F were single-cell sorted for antibody cloning. B cell reactivity with subtype A and subtype B is shown in the top and middle rows, respectively. The index sorting analysis is shown in the bottom panel. SSC-A, side scatter area; FSC-A, forward scatter area. FIG. 1 C shows the percentage of RSV F-specific, class-switched B cells for each infant ( FIG. 1 C ). Values were calculated based on flow cytometry data.

FIGS. 2 A- 2 E show that anti-RSV F antibodies isolated from infant B cells display limited somatic hypermutation (SHM) and biased V H and V L gene usage. A representative flow plot is shown for the RSV F-specific B cell response in an infant <3 months of age ( FIG. 2 A ) and an infant >6 months of age ( FIG. 2 B ). Prior to sorting on double positive staining with dual labeled RSV F probes, the plot was gated on CD3 − CD19 + CD20 + B cells ( FIG. 1 A ) or CD3 CD19 + CD20 + IgG/IgA + B cells ( FIG. 2 B ). RSV F-specific B cells are in the upper right quadrant of the plots. FIG. 2 C shows the results of index sort analysis of the surface markers expressed on B cells from which RSV F-reactive antibodies were isolated. FIG. 2 D shows the number of V H nucleotide substitutions for antibodies isolated from RSV F-specific class-switched B cells (the red bars indicate medians). In both FIG. 2 C and FIG. 2 D , infants are ordered from youngest to oldest, left to right. FIG. 2 E shows a heat map of V H and V L germline gene usage for all infants (left panel), showing only genes for which at least one V H /V L pairing was utilized in ≥0.5% of all antibodies isolated. The percent total of antibodies with the designated V H /V L pairing is provided (right panel).

FIGS. 3 A- 3 D show that a subset of RSV F-specific infant antibodies binds with high affinity to RSV F and neutralizes RSV. The fraction of isolated antibodies from each infant that binds with weak, low, medium, or high apparent affinity for preF ( FIG. 3 A ) or postF ( FIG. 3 B ) is shown for each antibody that displayed detectable binding in this assay. Infants are ordered from youngest to oldest, left to right. Apparent binding affinities are shown for each antibody. Black bars indicate medians. N.D., not determined. The percentage of antibodies isolated from each infant that shows weak, low, medium, or high neutralization potency is shown ( FIG. 3 C ). Neutralization IC 50 values are shown for each antibody with measurable neutralization activity. Top, middle, and bottom dotted lines show IC 50 values for motavizumab, MPE8, and D25, respectively. Black bars indicate medians. FIG. 3 D shows the apparent affinities for postF plotted against apparent affinities for preF for infants <3 months (left panel) and ≥6 months (right panel).

FIGS. 4 A- 4 C show that RSV-neutralizing, F-conformation-independent antibodies are rare in young infants. The percentage of antibodies that are preF-specific (black), preF- and postF-reactive (grey), or postF-specific (light grey) is shown for each infant ( FIG. 4 A ). N.D., not-determined (white). Infants are ordered from youngest to oldest, left to right. The percentage of antibodies with high, medium, low, or weak neutralization potency is plotted for each group in infants <3 mo. (left panel) and ≥6 mo. (right panel) ( FIG. 4 B ). Neutralization IC 50 s are shown for antibodies in each group that displayed measurable neutralization activity ( FIG. 4 C ). Black bars indicate medians. In FIGS. 4 B and 4 C , antibodies for which preF and postF binding affinities were measured are grouped according to preF or postF specificity.

FIGS. 5 A and 5 B show that polyreactivity of infant antibodies decreases with increasing levels of somatic hypermutation. The percent of antibodies with high, medium, low, or undetectable polyreactivity is shown for each infant ( FIG. 5 A ). Four panels of control antibodies, each with a variety of specificities, are shown for comparison: 364 RSV F-specific antibodies previously isolated from healthy adults, 138 antibodies currently in clinical trials, 39 antibodies that are approved for clinical use, and 14 broadly neutralizing HIV-1 antibodies. Infant antibodies are grouped according to the number of nucleotide mutations present in the VH gene ( FIG. 5 B ).

FIGS. 6 A- 6 C show that infant responses are focused toward two antigenic sites with different neutralization sensitivities. FIG. 6 A shows the preF structure with two protomers as grey molecular surfaces and one protomer as ribbons colored according to the antigenic site. FIG. 6 B shows the percentage of isolated antibodies that recognize each antigenic site, plotted for each donor. Infants are ordered from youngest to oldest, left to right. FIG. 6 C shows antibodies isolated from infants <3 months (left panel) and ≥6 months (right panel) grouped according to neutralization potency and antigenic site. N.N., non-neutralizing.

FIGS. 7 A- 7 E show antibodies directed towards sites I and III utilize convergent sequence features and preferentially bind to different conformations of RSV F. Heat map of VH and VL germline gene usage for all site I-directed antibodies for which at least one VH/VL pairing was used in ≥0.5% of the antibodies directed against site I ( FIG. 7 A ). A heat map of VH and VL germline gene usage for all site III-directed antibodies for which at least one VH/VL pairing was used in ≥0.5% of the antibodies directed against site III ( FIG. 7 B ). WebLogos showing the CDR H3 sequence motifs for site I-directed (top) and site III-directed (bottom) antibodies ( FIG. 7 C ). Apparent binding affinities for postF are plotted against apparent affinities for preF for antibodies directed against site I and site III ( FIG. 7 D , left panel). Antibodies that are preF-specific are boxed in. Apparent preF affinity for preF-specific antibodies is shown ( FIG. 7 D , right panel). Antibodies are grouped according to antigenic site and the percentage of antibodies in each group with high, medium, low, or weak neutralization potency is shown ( FIG. 7 E , left panel). Neutralization IC 50 s is plotted for the antibodies in each group with detectable neutralization activity ( FIG. 7 E , right panel). Top, middle, and bottom dotted lines show IC 50 s for motavizumab, MPE8 and D25, respectively.

FIGS. 8 A- 8 D show that germline antibodies targeting antigenic site III can potently neutralize RSV and are present in the naïve B cell repertoire. FIG. 8 A shows the neutralization potency (IC 50 ) of antibodies lacking VH or VL nucleotide substitutions, grouped according to antigenic site. Top, middle, and bottom dotted lines show the IC 50 value for motavizumab, MPE8, and D25, respectively. N.N., non-neutralizing. No antibodies against site Ø lacking substitutions were obtained. FIG. 8 B shows the results of index sort analysis of the surface markers expressed on cells from which RSV-reactive antibodies were isolated in infants <3 months. The percentage of B cells in each group is shown for all antibodies, neutralizing antibodies that lack somatic mutations (germline neut.), and neutralizing antibodies that contain somatic mutations (mutated neut.). FIG. 8 C contains pie charts showing the fraction of RSV F-reactive naïve B cells isolated from the cord blood of four donors (top panel) and peripheral blood from two donors (bottom panel) that utilized VH3-21/VL1-40 or VH3-11/VL1-40 germline gene pairing. Naïve B cells were defined as CD3 CD14 CD19 + CD20 + IgM + IgG − CD27 − cells. The number in the center of the pie (top and bottom) indicates the total number of antibodies with detectible binding to RSV F when produced as full-length IgG. FIG. 8 D shows the apparent affinity for preF for each of these antibodies and colored according to germline usage. Black bars indicate medians. IC 50 values for antibodies that displayed detectible neutralizing activity.

FIGS. 9 A- 9 D shows the non-neutralizing antibody ADI-14359 uses a convergent CDR H3 motif and germline features of the VK1-39 light chain for binding to antigenic site Ion postF. FIG. 9 A shows a crystal structure of infant antibody ADI-14359 (VH2-70/VK1-39) in complex with postF. FIG. 9 B shows a magnified view of the CDRH3 of ADI-14359 inserted into a groove on the surface of postF. The variable region of ADI-14359 and one RSV F protomer are shown as ribbons and the C-α atom of Pro389, a residue associated with viral escape from site I-directed antibodies, is shown as a sphere. FIG. 9 C shows a magnified view of the antibody interface, highlighting the features of the convergent CDR H3 motif that mediate recognition of site I (left panel), whereas a 180° rotation highlights the CDR H2 contacts made with postF (right panel). The sequence logo for the convergent CDR H3 motif is shown (generated using WebLogo, described by Crooks et al., 2004). FIG. 9 D shows the binding of ADI-14359 to postF as measured by surface plasmon resonance (top panel). Rate constants for the germline-reverted variant (R50L) binding to postF were too fast to be accurately determined (top middle panel) and, therefore, the equilibrium responses were plotted against the concentration of Fab and fit to a steady-state affinity model (bottom middle panel). Binding of ADI-14359 to the K390A variant of postF was too weak to determine an affinity (bottom panel).

FIGS. 10 A- 10 D show that the light chain mediates postF preference of ADI-14359. The crystal structure of ADI-14359 (VH2-70/VK1-39) in complex with postF is shown at a 180° rotation with respect to FIG. 9 ( FIG. 10 A ). Two protomers of postF are shown as molecular surfaces and the third protomer and ADI-14359 are shown as ribbons. The ADI-14359 heavy chain is gray and the light chain is white. The position of the fused viral and host-cell membranes is shown for orientation. The predicted interaction between preF and ADI-14359 was predicted by aligning the unbound preF structure to the ADI-14359-bound postF structure ( FIG. 10 B ). The unfused viral membrane is shown for orientation. A magnified view of the ADI-14359-postF interface ( FIG. 10 C ). One protomer is shown in ribbons. The ADI-14359 light chain CDR1 and FW3 form hydrogen bonds with two residues on β1 (Glu31 and Tyr33). A magnified view of the predicted ADI-14359-preF interface ( FIG. 10 D ). In preF, (322 blocks access to (31 and would clash with the ADI-14359 light chain FW3 and CDR1. In addition, Glu31 is rotated away from ADI-14359 in preF, which would prevent hydrogen bonding with this residue.

FIGS. 11 A- 11 C show that neutralizing antibody ADI-19425 uses germline-encoded features for high-affinity binding to antigenic site III on preF. FIG. 11 A shows a crystal structure of ADI-19425 in complex with preF viewed along (left panel) and above (right panel) the viral membrane. FIG. 11 B shows a magnified view of the interface with the variable region of ADI-19425 and one RSV F protomer shown in ribbon (left panel) and a 90-degree rotation showing the interactions between the light chain of ADI-19425 and the α6-α7 loop of antigenic site II (right panel). FIG. 11 C shows the binding of ADI-19425 and the Y33A, Y93A and Y56A variants to preF as measured by surface plasmon resonance.

FIGS. 12 A- 12 D show ADI-19425 and MPE8 utilize similar germline-encoded features to recognize preF. A ternary crystal structure of preF, 3 AM22 Fabs, and 3 ADI-19425 Fabs was generated ( FIG. 12 A , left and right panels). The right panel shows the same complex in the left panel, but rotated by 90° to show the view looking toward the viral membrane. Neutralization of two strains of RSV (A2 and B10895) by ADI-19425 IgG was measured using the fluorescence plate reader assay ( FIG. 12 B ). The preF-bound MPE8 Fv was aligned to preF bound by ADI-19425 ( FIG. 12 C , left and right panels). The right panel is rotated by 90° relative to the left panel to show the top view. The MPE8 Fv is aligned to that of ADI-19425 ( FIG. 12 D , left and right panels). The right panel shows the binding interface between preF and ADI-19425, with the same orientation shown in FIG. 11 B . The CDR loops are shown for both ADI-19425 and MPE8.

FIGS. 13 A-C show analysis of RSV F-specific B cell responses in the adenoids and peripheral blood of young children. RSV F-specific B cells were measured in adenoid and peripheral blood by flow cytometry ( FIG. 13 A , left, middle, and right panels). The left panel shows the frequency of RSV F-specific B cells among CD19 + B cells in adenoid for a representative donor. The middle panel shows the frequency of RSV F-specific B cells among CD19 + B cells in PBMCs for a representative donor. The frequency of RSV F-reactive B cells within the CD14 − CD3 − CD8 − CD19 + CD20 + population is shown next to the gate. The right panel shows a summary for all 6 donors analyzed. Index sort analysis of surface markers expressed on B cells from which RSV F-reactive antibodies were isolated ( FIG. 13 B ). Percentage of RSV F-reactive B cells within each memory B cell subset that express FCRL4 ( FIG. 13 C ). Asterisks indicate B cell responses that were below the limit of detection.

FIGS. 14 A-B show the lack of a clear correlation between the frequency of RSV F-reactive B cells in either compartment and serum neutralization titer. FIG. 14 A shows the percentage of RSV F-specific B cells among CD19 + B cells in the adenoids and PBMCs for a representative donor. FIG. 14 B shows the percentage of RSV F-specific B cells among CD19 + B cells in the adenoids (left panel) and in the PBMCs (right panel) for a representative donor.

FIGS. 15 A-C characterize the RSV-specific mucosal B cell response. FIG. 15 A shows that the RSV F-specific antibody repertoires were highly diverse in both compartments (adenoids and PBMCs) in all donors, each containing few to no expanded clonal lineages. FIG. 15 B shows the CDRH3 length distribution of the antibodies isolated from PBMCs and adenoids. FIG. 15 C shows a comparable VH germline gene usage between the two compartments, though there was an enrichment for VH5-51 and VH1-69 in the adenoid-derived antibodies and an enrichment for VH4-34 and VH3-30 in the PBMC-derived antibodies.

FIGS. 16 A-E show the level of somatic mutation in the antibodies was varied among the 4 donors. FIG. 16 A shows the median number of VH nucleotide substitutions ranged from 8-11 in the adenoid-derived antibodies and 7-9 in the PBMC-derived antibodies. **** indicates that the difference in number of substitutions in the adenoid-derived antibodies relative to the PBMC-derived antibodies reached statistical significance in Donor 2665. FIG. 16 B compares the levels of SHM within each individual B cell subset in adenoids (left panel) and PBMCs (right panel). FIG. 16 C shows the percentage of antibodies derived from IgG-IgA-CD27-peripheral blood B cells containing SHM. FIG. 16 D shows a subset of somatically mutated antibodies derived from IgG-IgA-CD27-peripheral blood B cells that contained lower levels of SHM compared to antibodies derived from IgG-IgA-CD27-adenoid B cells. FIG. 16 E shows the IgM and IgD expression profiles of RSV F-specific IgG-IgA-CD27-adenoid B cells.

FIGS. 17 A-D show the number of VH nucleotide substitutions in the adenoid-derived antibodies and PBMC-derived antibodies for each donor. FIG. 17 A shows the number of VH nucleotide substitutions for Donor 2635. FIG. 17 B shows the number of VH nucleotide substitutions for Donor 2665. **** indicates that the difference in number of substitutions in the adenoid-derived antibodies relative to the PBMC-derived antibodies reached statistical significance in Donor 2665. FIG. 17 C shows the number of VH nucleotide substitutions for Donor 2666. FIG. 17 D shows the number of VH nucleotide substitutions for Donor 2849.

FIGS. 18 A-B show the binding properties of the adenoid and PBMC-derived antibodies. FIG. 18 A shows the percentage of antibodies that bind RSV preF, postF, and preF & postF using biolayer interferometry. FIG. 18 B shows the percentage of antibodies that bind preF with weak (>50 nm), low (>5 to 50 nM), medium (>0.5 to 5 nM), and high (<0.5 nM) binding affinities.

FIGS. 19 A-D show the neutralizing activity of the adenoid and PBMC-derived antibodies against RSV-A2. FIG. 19 A shows the amount of detectable neutralizing activity (IC50<25 μg/mL) for adenoid and PBMC-derived antibodies using a luciferase-based assay. FIG. 19 B shows the neutralization actity of preF-specific antibodies, postF-specific antibodies, and preF and PostF reactive antibodies isolated from both adenoids and PBMCs. FIG. 19 C shows the memory B cell subsets for the adenoid-derived and PBMC-derived neutralizing antibodies. FIG. 19 D shows the apparent preF K D (left panel) and the virus neutralization IC50 for each memory B cell subset.

FIGS. 20 A-C shows the levels of polyreactivity and binding affinities of the antibodies derived from the adenoid and PBMC samples. FIG. 20 A shows the percentage of antibodies having low and high levels of polyreactivity. FIG. 20 B shows the percentage of low and high polyreactive clones across different B cell subsets within each compartment (left panel shows adenoid-derived antibodies and right panel shows PBMC-derived antibodies). FIG. 20 C shows the percentage of antibodies having no binding or low, medium, or high affinity to RSV F.

DETAILED DESCRIPTION OF THE INVENTION

The present disclosure relates anti-RSV F infant antibodies, compositions comprising such antibodies, and methods for obtaining and using such antibodies. In some embodiments, the antibodies are neutralizing antibodies and, thus, the anti-RSV F neutralizing antibodies and compositions comprising such antibodies can be used as a vaccine. For infants, in particular, the subject anti-RSV F antibodies may provide advantageous protection.

Definitions

In order that the present disclosure may be more readily understood, certain terms are first defined. As used in this application, except as otherwise expressly provided herein, each of the following terms shall have the meaning set forth below. Additional definitions are set forth throughout the application. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

As used herein, the term “about,” when used in reference to a particular recited numerical value, means that the value may vary from the recited value by no more than 1%. For example, as used herein, the expression “about 100” includes 99 and 101 and all values in between (e.g., 99.1, 99.2, 99.3, 99.4, etc.).

“Respiratory Syncytial Virus fusion glycoprotein”, also referred to as “RSV F”, is a type I transmembrane surface protein that has an N terminal cleaved signal peptide and a membrane anchor near the C terminus (Collins, P. L. et al., (1984), PNAS (USA) 81:7683-7687). The RSV F protein is synthesized as an inactive 67 KDa precursor denoted as F0 (Calder, L. J.; et al., Virology (2000), 277, 122-131. The F0 protein is activated proteolytically in the Golgi complex by a furin-like protease at two sites, yielding two disulfide linked polypeptides, F2 and F1, from the N and C terminal, respectively. There is a 27 amino acid peptide released called “pep27”. There are furin cleavage sites (FCS) on either side of the pep27 (Collins, P. L.; Mottet, G. (1991), J. Gen. Virol., 72: 3095-3101; Sugrue, R. J, et al. (2001), J. Gen. Virol., 82, 1375-1386). The F2 subunit consists of the Heptad repeat C (HRC), while the F1 contains the fusion polypeptide (FP), heptad repeat A (HRA), domain I, domain II, heptad repeat B (HRB), transmembrane (TM), and cytoplasmic domain (CP) (See Sun, Z. et al. Viruses (2013), 5:21 1-225). The RSV F protein plays a role in fusion of the virus particle to the host cell membrane by irreversible protein refolding from the labile prefusion conformation (herein referred to as “prelusion F” or “preF”) to the stable postfusion conformation (herein referred to as “postfusion F” or “postF”). RSV F is expressed on the surface of infected cells. Accordingly, it plays a role in cell to cell transmission of the virus and syncytia formation. The amino acid sequence of the RSV F protein is provided in GenBank as accession number AAX23994.

A stabilized variant of the PreF trimeric conformation of RSV F, termed “RSV-DS-Cav1” or “DS-Cav1” disclosed in, inter alia, Stewart-Jones et al., PLos One, Vol. 10(6)):e0128779. doi: 10.1371/journal.pone.0128779 and WO 2011/050168 was used in the identification, isolation, and characterization of the disclosed antibodies.

The term “laboratory strain” as used herein refers to a strain of RSV (subtype A or subtype B) that has been passaged extensively in in vitro cell culture. A “laboratory strain” can acquire adaptive mutations that may affect their biological properties. The term “clinical strain” as used herein refers to an RSV isolate (subtype A or subtype B), which is obtained from an infected individual and has been isolated and grown in tissue culture at low passage.

The term “IC 50 ” refers to the “half maximal inhibitory concentration”, which value measures the effectiveness of compound (e.g., anti-RSV F antibody) inhibition towards a biological or biochemical utility. This quantitative measure indicates the quantity required for a particular inhibitor to inhibit a given biological process by half. In certain embodiments, RSV virus neutralization potencies for anti-RSV neutralizing antibodies disclosed herein are expressed as neutralization IC 50 values.

The term “infant”, as used herein, generally refers to a young child between one month and one year (12 months) of age; however, it can also apply to a child older than 1 year (12 months). In one embodiment, the infant is at least (≥) 6 months of age. In another embodiment, the infant is under 3 months of age.

The term “subject”, as used herein, refers to a human or a nonhuman. The term “nonhuman” includes, but is not limited to, domestic animals (such as horses, dogs and cats) and livestock (such as cattle, sheep, swine, and poultry). In some embodiments, the subject is a human (and, more preferably, a human infant). The term “subject” may be interchangeably used with the term “patient” in the context of the present disclosure.

“Motavizumab”, also referred to as “NUMAX™”, is an enhanced potency RSV F-specific humanized monoclonal antibody derived by in vitro affinity maturation of the CDRs of the heavy and light chains of palivizumab. For reference purposes, the amino acid sequence of the NUMAX™ antibody is disclosed in U.S. Patent Publication 2003/0091584; U.S. Pat. No. 6,818,216; Wu et al., (2005) J. Mol. Bio. 350(1):126-144; and Wu, et al. (2007) J. Mol. Biol. 368:652-665.

“Palivizumab”, also referred to as “SYNAGIS®”, is a humanized anti-RSV F antibody with heavy and light chain variable domains having the amino acid sequences as set forth in U.S. Pat. Nos. 7,635,568 and 5,824,307. Palivizumab immunospecifically binds to the RSV F protein, and is currently FDA-approved for the passive immunoprophylaxis of serious RSV disease in high-risk children. It is administered intramuscularly at recommended monthly doses of 15 mg/kg of body weight throughout the RSV season (November through April in the northern hemisphere). SYNAGIS® is composed of 95% human and 5% murine antibody sequences. See also Johnson et al., (1997), J. Infect. Diseases 176:1215-1224.

“MPE8” is a human monoclonal antibody (MPE8), generated by Humabs BioMed SA, that binds to antigenic site III of RSV F and potently cross-neutralizes RSV and HMPV. For reference purposes, the amino acid sequence of the MPE8 antibody is disclosed in Corti et al., 2013.

“D25” is a human IgG1 kappa monoclonal antibody, developed by AIMM Therapeutics B.V. in partnership with MedImmune, which binds to antigenic site Ø on RSV F and neutralizes RSV with high efficiency. For reference purposes, the amino acid sequence of the D25 antibody is disclosed in U.S. Pat. No. 8,562,996.

As used herein, the terms “treat,” “treatment,” and “treating” refer to the reduction, alleviation, or amelioration of the progression, development, recurrence, severity, and/or duration of an upper and/or lower respiratory tract RSV infection or a symptom, complication, respiratory condition related thereto (such as pneumonia or bronchiolitis) resulting from the administration of one or more therapies (including, but not limited to, the administration of one or more prophylactic or therapeutic agents alone or in combination). In certain embodiments, such terms refer to the reduction or inhibition of the replication of RSV, the inhibition or reduction in the spread of RSV to other tissues or subjects (e.g., the spread to the lower respiratory tract), the inhibition or reduction of infection of a cell with a RSV, or the amelioration of one or more symptoms associated with an upper and/or lower respiratory tract RSV infection.

As used herein, the terms “prevent,” “preventing,” and “prevention” refer to the prevention or inhibition of the development or onset of an upper and/or lower respiratory tract RSV infection or a respiratory condition related thereto resulting from the administration of one or more therapies (including, but not limited to, the administration of one or more prophylactic or therapeutic agents alone or in combination).

The term “antibody” (“Ab”), as used herein, refers to an immunoglobulin molecule that binds specifically to an antigen and comprises four polypeptide chains, two heavy (H) chains and two light (L) chains interconnected by disulfide bonds (i.e., “full antibody molecules”) or an antigen-binding fragment thereof. Each heavy chain is comprised of a heavy chain variable region (“HCVR” or “V H ”) and a heavy chain constant region (comprised of domains C H 1, C H 2, and C H 3). Each light chain is comprised of a light chain variable region (“LCVR” or “V L ”) and a light chain constant region (C L ). The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen. The constant regions of the antibodies may mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (C1q) of the classical complement system.

The V H and V L regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDRs), interspersed with regions that are more conserved, termed framework regions (FRs). Each V H and V L is composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. In certain embodiments of the invention, the FRs of the antibody (or antigen binding fragment thereof) may be identical to the human germline sequences, or may be naturally or artificially modified. An amino acid consensus sequence may be defined based on a side-by-side analysis of two or more CDRs. Accordingly, the CDRs in a heavy chain are designated “CHRH1”, “CDRH2”, and “CDRH3”, respectively, and the CDRs in a light chain are designated “CDRL1”, “CDRL2”, and “CDRL3”.

Substitution of one or more CDR residues or omission of one or more CDRs is also possible. Antibodies have been described in the scientific literature in which one or two CDRs can be dispensed with for binding. Analysis of the contact regions between antibodies and their antigens, based on published crystal structures, concluded that only about one fifth to one third of CDR residues actually contact the antigen (Padlan et al. (1995 FASEB J. 9:133-139). Also, it has been shown that in many antibodies one or two CDRs had no amino acids in contact with an antigen (see also, Vajdos et al. 2002 J Mol Biol 320:415-428).

CDR residues not contacting antigen can be identified based on previous studies (for example, residues H60-H65 in CDRH2 are often not required), from regions of Kabat CDRs lying outside Chothia CDRs, by molecular modeling and/or empirically. If a CDR or residue(s) thereof is/are omitted, it is usually substituted with an amino acid occupying the corresponding position in another human antibody sequence or a consensus of such sequences. Positions for substitution within CDRs and amino acids to substitute can also be selected empirically.

The fully human monoclonal antibodies disclosed herein may comprise one or more amino acid substitutions, insertions and/or deletions in the framework and/or CDR regions of the heavy and light chain variable domains as compared to the corresponding germline sequences. Such mutations can be readily ascertained by comparing the amino acid sequences disclosed herein to germline sequences available from, for example, public antibody sequence databases. The present invention includes antibodies, and antigen-binding fragments thereof, that are derived from any of the amino acid sequences disclosed herein, wherein one or more amino acids within one or more framework and/or CDR regions are mutated to the corresponding residue(s) of the germline sequence from which the antibody was derived, or to the corresponding residue(s) of another human germline sequence, or to a conservative amino acid substitution of the corresponding germline residue(s) (such sequence changes are referred to herein collectively as “germline mutations”). A person of ordinary skill in the art, starting with the heavy and light chain variable region sequences disclosed herein, can easily produce numerous antibodies and antigen-binding fragments which comprise one or more individual germline mutations or combinations thereof. In certain embodiments, all of the framework and/or CDR residues within the V H and/or V L domains are mutated back to the residues found in the original germline sequence from which the antibody was derived. In other embodiments, only certain residues are mutated back to the original germline sequence, e.g., only the mutated residues found within the first 8 amino acids of FR1 or within the last 8 amino acids of FR4, or only the mutated residues found within CDR1, CDR2 or CDR3. In other embodiments, one or more of the framework and/or CDR residue(s) are mutated to the corresponding residue(s) of a different germline sequence (i.e., a germline sequence that is different from the germline sequence from which the antibody was originally derived). Furthermore, the antibodies of the present invention may contain any combination of two or more germline mutations within the framework and/or CDR regions, e.g., wherein certain individual residues are mutated to the corresponding residue of a particular germline sequence while certain other residues that differ from the original germline sequence are maintained or are mutated to the corresponding residue of a different germline sequence. Once obtained, antibodies and antigen-binding fragments that contain one or more germline mutations can be easily tested for one or more desired property such as, improved binding specificity, increased binding affinity, improved or enhanced antagonistic or agonistic biological properties (as the case may be), reduced immunogenicity, etc. Antibodies and antigen-binding fragments obtained in this general manner are encompassed within the present invention.

An immunoglobulin may derive from any of the commonly known isotypes, including but not limited to IgA, secretory IgA, IgG, and IgM. IgG subclasses are well known to those in the art and include, but are not limited to, human IgG1, IgG2, IgG3, and IgG4. “Isotype” refers to the antibody class or subclass (e.g., IgG1) that is encoded by the heavy chain constant region genes. The term “antibody” includes, by way of example, both naturally occurring and non-naturally occurring antibodies; monoclonal antibodies (“mAb”) and polyclonal antibodies; chimeric and humanized antibodies; human or non-human antibodies; wholly synthetic antibodies; and single chain antibodies. Where not expressly stated, and unless the context indicates otherwise, the term “antibody” includes an antigen-binding fragment or an antigen-binding portion of any of the aforementioned immunoglobulins, a monovalent and a divalent fragment or portion, and a single chain antibody.

The term “human antibody”, as used herein, is intended to include antibodies having variable and constant regions derived from human germline immunoglobulin sequences (and, thus, does not include antibodies in which CDRs derived from the germline of another mammalian species (e.g., mouse) have been grafted onto human FR sequences). The human antibodies of the invention may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo), for example in the CDRs, in particular CDR3.

The term “humanized antibody”, as used herein, refers to a human antibody in which one or more CDRs have been replaced with one or more corresponding CDRs obtained a non-human derived (e.g., mouse, rat, rabbit, primate) antibody. Humanized antibodies may also include certain non-CDR sequences or residues derived from such non-human antibodies as well as the one or more non-human CDR sequence. Such antibodies may also be referred to as “chimeric antibodies”.

The term “recombinant” generally refers to any protein, polypeptide, or cell expressing a gene of interest that is produced by genetic engineering methods. The term “recombinant” as used herein with respect to a protein or polypeptide, means a polypeptide produced by expression of a recombinant polynucleotide. The proteins used in the immunogenic compositions of the invention may be isolated from a natural source or produced by genetic engineering methods.

The antibodies of the invention may, in some embodiments, be recombinant human antibodies. The term “recombinant human antibody”, as used herein, is intended to include all antibodies (including human or humanized antibodies) that are prepared, expressed, created, or isolated by recombinant means, such as antibodies expressed using a recombinant expression vector transfected into a host cell (described further below); antibodies isolated from a recombinant, combinatorial human antibody library (described further below); antibodies isolated from an animal (e.g., a mouse) that is transgenic for human immunoglobulin genes (see, e.g., Taylor et al. (1992) Nucl. Acids Res. 20:6287-6295); or antibodies prepared, expressed, created or isolated by any other means that involve splicing of human immunoglobulin gene sequences to other DNA sequences. Such recombinant human antibodies have variable and constant regions derived from human germline immunoglobulin sequences. In certain embodiments, however, such recombinant human antibodies are subjected to in vitro mutagenesis (or, when an animal transgenic for human Ig sequences is used, in vivo somatic mutagenesis) and thus the amino acid sequences of the V H and V L regions of the recombinant antibodies are sequences that, while derived from and related to human germline V H and V L sequences, may not naturally exist within the human antibody germline repertoire in vivo.

The terms “specifically binds” or “binds specifically to” are used interchangeably and mean that an antibody or antigen-binding fragment thereof forms a complex with an antigen that is relatively stable under physiologic conditions. Specific binding can be characterized by an equilibrium dissociation constant of at least about 1×10 −6 M or less (e.g., a smaller K D denotes a tighter binding). Methods for determining whether two molecules specifically bind are well known in the art and include, for example, equilibrium dialysis, surface plasmon resonance, and the like. As described herein, antibodies have been identified by surface plasmon resonance, e.g., BIACORE™, biolayer interferometry measurements using, e.g., a ForteBio Octet HTX instrument (Pall Life Sciences), which bind specifically to RSV F. Moreover, multi-specific antibodies that bind to RSV F protein and one or more additional antigens, or a bi-specific that binds to two different regions of RSV F, are nonetheless considered antibodies that “specifically bind”. In certain embodiments, the antibodies disclosed herein display equilibrium dissociation constants (and hence specificities) of about 1×10 −6 M; about 1×10 −7 M; about 1×10 −8 M; about 1×10 −9 M; about 1×10 −10 M about 1×10 −11 M; about 1×10 −12 M; between about 1×10 −7 M and about 1×10 −11 M; or between about 1×10 −8 M and about 1×10 −10 M.

The term “high affinity antibody” refers to those antibodies having a binding affinity to RSV F (preF or postF) of about ≤0.5 nM as measured by surface plasmon resonance, e.g., BIACORE™, biolayer interferometry measurements using, e.g., a ForteBio Octet HTX instrument (Pall Life Sciences).

The term “medium affinity antibody” refers to those antibodies having a binding affinity to RSV F of about >0.5 to 5 nM as measured by surface plasmon resonance, e.g., BIACORE™, biolayer interferometry measurements using, e.g., a ForteBio Octet HTX instrument (Pall Life Sciences).

The term “low affinity antibody” refers to those antibodies having a binding affinity to RSV F of about >5 to 50 nM as measured by surface plasmon resonance, e.g., BIACORE™, biolayer interferometry measurements using, e.g., a ForteBio Octet HTX instrument (Pall Life Sciences).

The term “weak affinity antibody” refers to those antibodies having a binding affinity to RSV F of about >50 nM as measured by surface plasmon resonance, e.g., BIACORE™, biolayer interferometry measurements using, e.g., a ForteBio Octet HTX instrument (Pall Life Sciences).

The terms “antigen-binding portion” and “antigen-binding fragment” are used interchangeably and refer to any naturally occurring, enzymatically obtainable, synthetic, or genetically engineered polypeptide or glycoprotein that specifically binds an antigen to form a complex. In certain embodiments, the terms “antigen-binding portion” and “antibody fragment” refer to one or more fragments of an antibody that retains the ability to bind to RSV F.

An antibody fragment may include a Fab fragment, a F(ab′)2 fragment, a Fv fragment, a dAb fragment, a fragment containing a CDR, or an isolated CDR. Antigen-binding fragments of an antibody may be derived, e.g., from full antibody molecules using any suitable standard techniques such as proteolytic digestion or recombinant genetic engineering techniques involving the manipulation and expression of DNA encoding antibody variable and (optionally) constant domains. Such DNA is known and/or is readily available from, e.g., commercial sources, DNA libraries (including, e.g., phage-antibody libraries), or can be synthesized. The DNA may be sequenced and manipulated chemically or by using molecular biology techniques, for example, to arrange one or more variable and/or constant domains into a suitable configuration, or to introduce codons, create cysteine residues, modify, add, or delete amino acids, etc.

Non-limiting examples of antigen-binding fragments include: (i) Fab fragments; (ii) F(ab′)2 fragments; (iii) Fd fragments; (iv) Fv fragments; (v) single-chain Fv (scFv) molecules; (vi) dAb fragments; and (vii) minimal recognition units consisting of the amino acid residues that mimic the hypervariable region of an antibody (e.g., an isolated complementarity determining region (CDR) such as a CDR3 peptide), or a constrained FR3-CDR3-FR4 peptide. Other engineered molecules, such as domain-specific antibodies, single domain antibodies, domain-deleted antibodies, chimeric antibodies, CDR-grafted antibodies, diabodies, triabodies, tetrabodies, minibodies, nanobodies (e.g., monovalent nanobodies, bivalent nanobodies, etc.), small modular immunopharmaceuticals (SMIPs), and shark variable IgNAR domains, are also encompassed by “antigen-binding fragment” and “antigen-binding portion”.

An antigen-binding fragment of an antibody will typically comprise at least one variable domain. The variable domain may be of any size or amino acid composition and will generally comprise at least one CDR, which is adjacent to or in frame with one or more framework sequences. In antigen-binding fragments having a V H domain associated with a V L domain, the V H and V L domains may be situated relative to one another in any suitable arrangement. For example, the variable region may be dimeric and contain V H -V H , V H -V L , or V L -V L dimers. Alternatively, the antigen-binding fragment of an antibody may contain a monomeric V H or V L domain.

In certain embodiments, an antigen-binding fragment of an antibody may contain at least one variable domain covalently linked to at least one constant domain. Non-limiting, exemplary configurations of variable and constant domains that may be found within an antigen-binding fragment of an antibody of the present invention include: (i) V H -C H 1; (ii) V H -C H 2; (iii) V H -C H 3; (iv) V H -C h 1-C h 2; (v) V H -C h 1-C h 2-C h 3; (vi) V H -C H 2-C H 3; (vii) V H -C L ; (viii) V L -C H 1; (ix) V L -C H 2; (x) V L -C H 3; (xi) V L -C H 1-C H 2; (xii) V L -C H 1-C H 2-C H 3; (xiii) V L -C H 2-C H 3; and (xiv) V L -C L . In any configuration of variable and constant domains, including any of the exemplary configurations listed above, the variable and constant domains may be either directly linked to one another or may be linked by a full or partial hinge or linker region. A hinge region may consist of at least 2 (e.g., 5, 10, 15, 20, 40, 60 or more) amino acids, which result in a flexible or semi-flexible linkage between adjacent variable and/or constant domains in a single polypeptide molecule. Moreover, an antigen-binding fragment of an antibody of the present invention may comprise a homo-dimer or hetero-dimer (or other multimer) of any of the variable and constant domain configurations listed above in non-covalent association with one another and/or with one or more monomeric V H or V L domain (e.g., by disulfide bond(s)).

As with full antibody molecules, antigen-binding fragments may be mono-specific or multi-specific (e.g., bi-specific). A multi-specific antigen-binding fragment of an antibody typically comprises at least two different variable domains, wherein each variable domain is capable of specifically binding to a separate antigen or to a different epitope on the same antigen. Any multi-specific antibody format, including the exemplary bi-specific antibody formats disclosed herein, may be adapted for use in the context of an antigen-binding fragment of an antibody of the present invention using routine techniques available in the art.

In certain embodiments, the antibody or antibody fragment is mono-specific, bi-specific, or multi-specific. Multi-specific antibodies may be specific for different epitopes of one target polypeptide or may contain antigen-binding domains specific for epitopes of more than one target polypeptide. An exemplary bi-specific antibody format that can be used in the context of the present invention involves the use of a first immunoglobulin (Ig) C H 3 domain and a second Ig C H 3 domain, wherein the first and second Ig C H 3 domains differ from one another by at least one amino acid, and wherein at least one amino acid difference reduces binding of the bi-specific antibody to Protein A as compared to a bi-specific antibody lacking the amino acid difference. In one embodiment, the first Ig C H 3 domain binds Protein A and the second Ig C H 3 domain contains a mutation that reduces or abolishes Protein A binding such as an H95R modification (by IMGT exon numbering; H435R by EU numbering). The second C H 3 may further comprise an Y96F modification (by IMGT; Y436F by EU). Further modifications that may be found within the second C H 3 include: D16E, L18M, N44S, K52N, V57M, and V82I (by IMGT; D356E, L358M, N384S, K392N, V397M, and V422I by EU) in the case of IgG1 monoclonal antibodies; N44S, K52N, and V82I (IMGT; N384S, K392N, and V422I by EU) in the case of IgG2 monoclonal antibodies; and Q15R, N44S, K52N, V57M, R69K, E79Q, and V82I (by IMGT; Q355R, N384S, K392N, V397M, R409K, E419Q, and V422I by EU) in the case of IgG4 monoclonal antibodies. Variations of these bi-specific antibody formats are also encompassed within the scope of the present invention.

The antibodies provided herein can be derivatized or linked to another functional molecule (e.g., another peptide or protein). Accordingly, the antibodies of the invention are intended to include derivatized and otherwise modified forms of the anti-RSV F antibodies described herein. For example, an antibody can be functionally linked (e.g., by chemical coupling, genetic fusion, noncovalent association or otherwise) to one or more other molecular entities, such as another antibody (e.g., a bispecific antibody or a diabody), a detectable agent, a cytotoxic agent, a pharmaceutical agent, and/or a protein or peptide that can mediate associate of the antibody or antibody portion with another molecule (such as a streptavidin core region or a polyhistidine tag).

One type of derivatized antibody is produced by crosslinking two or more antibodies (of the same type or of different types, e.g., to create bispecific antibodies, which is also discussed below).

Exemplary detectable agents with which an antibody of the invention may be derivatized include fluorescent compounds (such as, but not limited to, fluorescein, fluorescein isothiocyanate, rhodamine, 5-dimethylamine-1-napthalenesulfonyl chloride, phycoerythrin and the like). An antibody may also be derivatized with detectable enzymes (such as, but not limited to, alkaline phosphatase, horseradish peroxidase, glucose oxidase and the like). When an antibody is derivatized with a detectable enzyme, it can be detected by adding additional reagents that the enzyme uses to produce a detectable reaction product (e.g., when the detectable agent horseradish peroxidase is present, the addition of hydrogen peroxide and diaminobenzidine leads to a colored reaction product, which is detectable). An antibody may also be derivatized with biotin, and detected through indirect measurement of avidin or streptavidin binding. Such derivatized anti-RSV F antibodies may be useful for the detection and/or diagnosis of RSV in a subject.

The specific embodiments, antibodies, or antibody fragments of the invention may be conjugated to a therapeutic moiety (“immunoconjugate”), such as an antibiotic, a second anti-RSV F antibody, a vaccine, a toxoid, or any other therapeutic moiety useful for treating an RSV infection.

The antibodies of the invention can also be modified by pegylation. An antibody can be pegylated to, for example, increase the biological (e.g., serum) half-life of the antibody. To pegylate, an antibody typically is reacted with a polyethylene glycol (PEG) reagent, such as a reactive ester or aldehyde derivative of PEG, under conditions in which one or more PEG groups become attached to the antibody or antibody fragment. Preferably, the pegylation is carried out via an acylation reaction or an alkylation reaction with a reactive PEG molecule (or an analogous reactive water-soluble polymer). As used herein, the term “polyethylene glycol” is intended to encompass any of the forms of PEG that have been used to derivatize other proteins, such as mono (C1-C10) alkoxy- or aryloxy-polyethylene glycol or polyethylene glycol-maleimide. In certain embodiments, the antibody to be pegylated is an aglycosylated antibody. Methods for pegylating proteins are known in the art and can be applied to the antibodies described herein. See for example, EP 0154316 by Nishimura et al. and EP 0401384 by Ishikawa et al.

The term an “isolated antibody”, as used herein, is intended to refer to an antibody that is substantially free of other antibodies having different antigenic specificities (e.g., an isolated antibody that specifically binds RSV F, or a fragment thereof, is substantially free of antibodies that specifically bind antigens other than RSV F).

The term a “blocking antibody” or a “neutralizing antibody”, as used herein (or an “antibody that neutralizes RSV F”), is intended to refer to an antibody whose binding to RSV F results in inhibition of at least one biological activity of RSV F. For example, such an antibody may aid in blocking the fusion of RSV to a host cell, prevent syncytia formation, and/or prevent the primary disease caused by RSV. Alternatively, or in addition, such an antibody may demonstrate the ability to ameliorate at least one symptom of the RSV infection. This inhibition of the biological activity of RSV F can be assessed by measuring one or more indicators of RSV F biological activity using standard in vitro assays (such as a neutralization assay) or in vivo assays known in the art (such as animal models to look at protection from challenge with RSV following administration of one or more of the antibodies described herein).

The term “surface plasmon resonance”, as used herein, refers to an optical phenomenon that allows for the analysis of real-time biomolecular interactions by detection of alterations in protein concentrations within a biosensor matrix, for example using the BIACORE™ system (Pharmacia Biosensor AB, Uppsala, Sweden and Piscataway, N.J.).

The term “K D ”, as used herein, is intended to refer to the equilibrium dissociation constant of a particular antibody-antigen interaction.

The term “epitope”, as used herein, refers to an antigenic determinant that interacts with a specific antigen binding site in the variable region of an antibody molecule known as a paratope. A single antigen may have more than one epitope. Thus, different antibodies may bind to different areas on an antigen and may have different biological effects. The term “epitope” also refers to a site on an antigen to which B and/or T cells respond. It also refers to a region of an antigen that is bound by an antibody. Epitopes may be defined as structural or functional. Functional epitopes are generally a subset of the structural epitopes and have those residues that directly contribute to the affinity of the interaction. Epitopes may also be conformational, that is, composed of non-linear amino acids. In certain embodiments, epitopes may include determinants that are chemically active surface groupings of molecules such as amino acids, sugar side chains, phosphoryl groups, or sulfonyl groups, and, in certain embodiments, may have specific three-dimensional structural characteristics, and/or specific charge characteristics.

The terms “substantial identity” and “substantially identical” are used interchangeably herein and, when referring to a nucleic acid or fragment thereof, indicates that, when optimally aligned with appropriate nucleotide insertions or deletions with another nucleic acid (or its complementary strand), there is nucleotide sequence identity in at least about 90%, and more preferably at least about 95%, 96%, 97%, 98%, or 99% of the nucleotide bases, as measured by any well-known algorithm of sequence identity, such as FASTA, BLAST, or GAP, as discussed below. Accordingly, nucleic acid sequences that display a certain percentage identity share that percentage identity and/or are that percentage identical to one another. A nucleic acid molecule having substantial identity to a reference nucleic acid molecule may, in certain instances, encode a polypeptide having the same or substantially similar amino acid sequence as the polypeptide encoded by the reference nucleic acid molecule.

In certain embodiments, the disclosed antibody nucleic acid sequences are, e.g., at least 70% identical; at least 75% identical; 80% identical; at least 85% identical; at least 90% identical; at least 95% identical; at least 96% identical; at least 97% identical; at least 98% identical; at least 99%; and/or all percentages of identity in between, to other sequences and/or share such percentage identities with one another (or with certain subsets of the herein-disclosed antibody sequences).

As applied to polypeptides, the term “substantial identity” or “substantially identical” means that two peptide sequences, when optimally aligned, such as by the programs GAP or BESTFIT using default gap weights, share at least 90% sequence identity, even more preferably at least 95%, 96%, 97%, 98%, or 99% sequence identity. Accordingly, amino acid sequences that display a certain percentage identity share that percentage identity and/or are that percentage identical to one another. Accordingly, amino acid sequences that display a certain percentage identity share that percentage identity and/or are that percentage identical to one another.

In certain embodiments, the disclosed antibody amino acid sequences are, e.g., at least 70% identical; at least 75% identical; 80% identical; at least 85% identical; at least 90% identical; at least 95% identical; at least 96% identical; at least 97% identical; at least 98% identical; at least 99%; and/or all percentages of identity in between, to other sequences and/or share such percentage identities with one another (or with certain subsets of the herein-disclosed antibody sequences).

Preferably, residue positions, which are not identical, differ by conservative amino acid substitutions. A “conservative amino acid substitution” is one in which an amino acid residue is substituted by another amino acid residue having a side chain (R group) with similar chemical properties (e.g., charge or hydrophobicity). In general, a conservative amino acid substitution will not substantially change the functional properties of a protein. In cases where two or more amino acid sequences differ from each other by conservative substitutions, the percent or degree of similarity may be adjusted upwards to correct for the conservative nature of the substitution. Means for making this adjustment are well known to those of skill in the art. (See, e.g., Pearson (1994) Methods Mol. Biol. 24: 307-331). Examples of groups of amino acids that have side chains with similar chemical properties include: 1) aliphatic side chains: glycine, alanine, valine, leucine and isoleucine; 2) aliphatic-hydroxyl side chains: serine and threonine; 3) amide-containing side chains: asparagine and glutamine; 4) aromatic side chains: phenylalanine, tyrosine, and tryptophan; 5) basic side chains: lysine, arginine, and histidine; 6) acidic side chains: aspartate and glutamate, and 7) sulfur-containing side chains: cysteine and methionine. Preferred conservative amino acids substitution groups are: valine-leucine-isoleucine, phenylalanine-tyrosine, lysine-arginine, alanine-valine, glutamate-aspartate, and asparagine-glutamine. Alternatively, a conservative replacement is any change having a positive value in the PAM250 log-likelihood matrix disclosed in Gonnet et al. (1992) Science 256: 1443 45. A “moderately conservative” replacement is any change having a non-negative value in the PAM250 log-likelihood matrix.

Sequence similarity for polypeptides is typically measured using sequence analysis software. Protein analysis software matches similar sequences using measures of similarity assigned to various substitutions, deletions and other modifications, including conservative amino acid substitutions. For instance, GCG software contains programs such as GAP and BESTFIT which can be used with default parameters to determine sequence homology or sequence identity between closely related polypeptides, such as homologous polypeptides from different species of organisms or between a wild type protein and a mutein thereof. See, e.g., GCG Version 6.1. Polypeptide sequences also can be compared using FASTA with default or recommended parameters; a program in GCG Version 6.1. FASTA (e.g., FASTA2 and FASTA3) provides alignments and percent sequence identity of the regions of the best overlap between the query and search sequences (Pearson (2000) supra). Another preferred algorithm when comparing a sequence of the invention to a database containing a large number of sequences from different organisms is the computer program BLAST, especially BLASTP or TBLASTN, using default parameters. (See, e.g., Altschul et al. (1990) J. Mol. Biol. 215: 403 410 and (1997) Nucleic Acids Res. 25:3389 402).

The phrase “therapeutically effective amount” refers to an amount of a therapeutic agent (e.g., an anti-RSV F antibody disclosed herein) that, when used alone or in combination with another therapeutic agent, protects a subject against the onset of a disease or promotes disease regression evidenced by a decrease in severity of disease symptoms, an increase in frequency and duration of disease symptom-free periods, or a prevention of impairment or disability due to the disease affliction. The ability of a therapeutic agent to promote disease regression can be evaluated using a variety of methods known to the skilled practitioner, such as in human subjects during clinical trials, in animal model systems predictive of efficacy in humans, or by assaying the activity of the agent in in vitro assays. The exact amount will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques (see, for example, Lloyd (1999) The Art, Science and Technology of Pharmaceutical Compounding).

The term “immunogenic composition” refers to a composition containing an antigen/immunogen, e.g., a microorganism (such as a virus or a bacterium) or a component thereof, a protein, a polypeptide, a fragment of a protein or polypeptide, a whole cell inactivated, subunit or attenuated virus, a polysaccharide, or combination thereof, that is administered to stimulate the recipient's humoral and/or cellular immune systems to one or more of the antigens/immunogens present in the immunogenic composition. The immunogenic compositions of the present invention can be used to treat a human susceptible to RSV infection, or suspected of having or being susceptible to RSV infection, by means of administering the immunogenic compositions via a systemic route. These administrations can include injection via the intramuscular (i.m.), intradermal (i.d.), intranasal, inhalation, or subcutaneous (s.c.) routes; application by a patch or other transdermal delivery device. In one embodiment, the immunogenic composition may be used in the manufacture of a vaccine or in the elicitation of polyclonal or monoclonal antibodies that could be used to passively protect or treat a subject.

The terms “vaccine” or “vaccine composition”, which are used interchangeably, refer to a composition comprising at least one immunogenic composition that induces an immune response in a subject (e.g., a mammal, e.g., a human).

In certain embodiments, a protein of interest comprises an antigen. The terms “antigen,” “immunogen,” “antigenic,” “immunogenic,” “antigenically active,” and “immunologically active”, when made in reference to a molecule, refer to any substance that is capable of inducing a specific humoral and/or cell-mediated immune response. In one embodiment, the antigen comprises an epitope.

“Immunologically protective amount”, as used herein, is an amount of an antigen effective to induce an immunogenic response in the recipient that is adequate to prevent or ameliorate signs or symptoms of disease, including adverse health effects or complications thereof. Either humoral immunity or cell-mediated immunity or both can be induced. The immunogenic response of an animal to a composition can be evaluated, e.g., indirectly through measurement of antibody titers, lymphocyte proliferation assays, or directly through monitoring signs and symptoms after challenge with the microorganism. The protective immunity conferred by an immunogenic composition or vaccine can be evaluated by measuring, e.g., reduction of shed of challenge organisms, reduction in clinical signs such as mortality, morbidity, temperature, and overall physical condition, health and performance of the subject. The immune response can comprise, without limitation, induction of cellular and/or humoral immunity. The amount of a composition or vaccine that is therapeutically effective can vary, depending on the particular organism used, or the condition of the animal being treated or vaccinated.

The terms “immune response” or “immunological response”, as used herein, refer to the development of a humoral immune response, a cellular-immune response, or a humoral and a cellular immune response to an antigen/immunogen. A “humoral immune response” refers to one that is, at least in part, mediated by antibodies. A “cellular immune response” is one mediated by T-lymphocytes and/or other white blood cells and includes the production of cytokines, chemokines, and similar molecules produced by activated T-cells and/or white blood cells. Immune responses can be determined using standard immunoassays and neutralization assays, which are known in the art.

The term “immunogenicity”, as used herein, refers to the capability of a protein or polypeptide to elicit an immune response directed specifically against a bacteria or virus that causes the identified disease.

Preparation of Human Antibodies

As disclosed herein, anti-RSV F infant antibodies may be obtained through B cell sorting techniques available to the artisan as well as those methods exemplified in the EXAMPLES below. Methods for generating human antibodies in transgenic mice are also known in the art and may also be employed to derive antibodies in accordance with the present disclosure. Any such known methods can be used in the context of the present invention to make human antibodies that specifically bind to RSV F (see, for example, U.S. Pat. No. 6,596,541).

The antibodies of the instant invention can possess affinities (K D ) ranging from about 1.0×10 −7 M to about 1.0×10 −12 M, when measured by binding to antigen either immobilized on solid phase or in solution phase. In some embodiments, the antibodies of the invention possess affinities (K D ) ranging from about 1×10 −7 M to about 1×10 −10 M, when measured by binding to antigen either immobilized on solid phase or in solution phase. In other embodiments, the antibodies of the invention possess a K D of less than 50 nM, 25 nM, 10 nM, 5 nM, 1 nM, 0.5 nM, or 0.1 nM, as measured by surface plasmon resonance.

The anti-RSV F antibodies and antibody fragments of the instant invention encompass proteins having amino acid sequences that may vary from the sequences of the described antibodies but, nonetheless, retain the ability to bind (and, in some cases, neutralize) RSV F. Such variant antibodies and antibody fragments comprise one or more additions, deletions, or substitutions of amino acids when compared to a parent sequence (i.e., amino acid sequence of a described antibody), but exhibit biological activity that is essentially equivalent to that of the described antibodies. Likewise, the antibody-encoding DNA sequences of the present invention encompass sequences that comprise one or more additions, deletions, or substitutions of nucleotides when compared to the disclosed sequence, but that encode an antibody or antibody fragment that is essentially bioequivalent to an antibody or antibody fragment described herein.

Two antigen-binding proteins (e.g., antibodies) are considered bioequivalent if, for example, they are pharmaceutical equivalents or pharmaceutical alternatives whose rate and extent of absorption do not show a significant difference when administered at the same molar dose under similar experimental conditions, either single does or multiple dose. Some antibodies will be considered equivalents or pharmaceutical alternatives if they are equivalent in the extent of their absorption but not in their rate of absorption and yet may be considered bioequivalent because such differences in the rate of absorption are intentional and are reflected in the labeling, are not essential to the attainment of effective body drug concentrations on, e.g., chronic use, and are considered medically insignificant for the particular drug product studied.

In one embodiment, two antigen-binding proteins (e.g., antibodies) are bioequivalent if there are no clinically meaningful differences in their safety, purity, and/or potency.

In another embodiment, two antigen-binding proteins (e.g., antibodies) are bioequivalent if a patient can be switched one or more times between the proteins (e.g., antibodies) without an expected increase in the risk of adverse effects, including a clinically significant change in immunogenicity, or diminished effectiveness, as compared to continued therapy without such switching.

In yet another embodiment, two antigen-binding proteins (e.g., antibodies) are bioequivalent if both proteins (e.g., antibodies) act by a common mechanism or mechanisms of action for the condition or conditions of use, to the extent that such mechanisms are known.

Bioequivalence may be demonstrated by in vivo and/or in vitro methods. Bioequivalence measures include, e.g., (a) an in vivo test in humans or other mammals, in which the concentration of the antibody or its metabolites is measured in blood, plasma, serum, or other biological fluid as a function of time; (b) an in vitro test that has been correlated with and is reasonably predictive of human in vivo bioavailability data; (c) an in vivo test in humans or other mammals in which the appropriate acute pharmacological effect of the antibody (or its target) is measured as a function of time; and (d) a well-controlled clinical trial that establishes safety, efficacy, bioavailability, and/or bioequivalence of an antibody.

Bioequivalent variants of the antibodies of the invention may be constructed by, for example, making various substitutions of residues or sequences or deleting terminal or internal residues or sequences (which may occur in the variable or binding regions as well as framework regions) not needed for biological activity. In some embodiments, it is contemplated that the anti-RSV F antibodies may contain inter alia one or more additional amino acid residue substitutions, mutations and/or modifications in the constant region (i.e., the Fc region) which result in preferred characteristics including, but not limited to: altered pharmacokinetics, increased serum half life, increase binding affinity, reduced immunogenicity, increased production, altered Fc ligand binding to an Fc receptor (FcR), enhanced or reduced ADCC (antibody-dependent cell mediated cytotoxicity) or CDC (complement-dependent cytotoxicity) activity, altered glycosylation and/or disulfide bonds and modified binding specificity. In this regard it will be appreciated that these Fc variants may advantageously be used to enhance the effective anti-neoplastic properties of the disclosed modulators. For example, cysteine residues not essential for biological activity can be deleted or replaced with other amino acids to prevent formation of unnecessary or incorrect intramolecular disulfide bridges upon renaturation. In other contexts, bioequivalent antibodies may include antibody variants comprising amino acid changes that modify the glycosylation characteristics of the antibodies, e.g., mutations that eliminate or remove glycosylation. In still other contexts, bioequivalent antibodies may include antibody variants comprising amino acid changes that modify the Fc region. Such Fc variant may have increased half-life, improved stability, and/or modified effector function(s).

Biological and Biophysical Characteristics of the Antibodies

In certain embodiments, the antibodies and antigen-binding fragments thereof specifically bind to RSV F, wherein at least one of the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and/or CDRL3 amino acid sequences of such antibody or the antigen-binding fragment thereof is at least 70% identical; at least 75% identical; 80% identical; at least 85% identical; at least 90% identical; at least 95% identical; at least 96% identical; at least 97% identical; at least 98% identical; at least 99%; and/or all percentages of identity in between, to at least one of the CDRH1, a CDRH2, a CDRH3, a CDRL1, a CDRL2, and/or a CDRL3 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

Without wishing to be bound by any theory, it is believed that the inventive antibodies and antigen-binding fragments thereof may function by binding to RSV F, preferably in the PreF conformation, and in so doing act to block the fusion of the viral membrane with the host cell membrane. The antibodies of the present invention may also function by binding to RSV F and in so doing block the cell to cell spread of the virus and block syncytia formation associated with RSV infection of cells. Subtype A is responsible for the majority of hospitalizations for RSV and RSV-related complications. Advantageously, RSV subtype A or both RSV subtype A and RSV subtype B are effectively blocked, or neutralized, by the majority of the anti-RSV antibodies disclosed herein.

In certain embodiments, the inventive antibodies and antigen-binding fragment thereof display better binding affinity for the prefusion (PreF) form of RSV F relative to the postfusion (PostF) form of RSV F. Indeed, in some embodiments, the anti-RSV F antibodies disclosed herein bind to PreF (e.g., with high affinity) but do not bind to PostF or bind to PostF with low affinity. In other embodiments, the antibodies and antigen-binding fragments thereof disclosed herein display better binding affinity for PostF than PreF.

Antibodies with a range of polyreactivity (high, medium, low, or undetectable) are disclosed. In some embodiments, the inventive antibodies and antigen-binding fragments thereof advantageously display a clean or low polyreactivity profile (see, e.g., WO 2014/179363 and Xu et al., Protein Eng Des Sel , Oct; 26(10):663-70. doi: 10.1093/protein/gzt047), and are thus particularly amenable to development as safe, efficacious, and developable therapeutic and/or prophylactic anti-RSV treatments.

In certain embodiments, the inventive antibodies and antigen-binding fragments thereof, without wishing to be bound by any theory, may function by blocking or inhibiting RSV fusion to the cell membrane by binding to any one or more of antigenic Sites Ø, I, II, III, IV, and/or Site V of the F protein. In certain embodiments, the antibodies disclosed herein display antigenic site specificity for Site III of (preF) RSV F and, generally, such antibodies are neutralizing antibodies (in some instances, e.g., ADI-19425, potently neutralizing). In other embodiments, the antibodies disclosed herein display antigenic site specificity for Site I of (postF) RSV F and, generally, such antibodies are non-neutralizing antibodies.

In certain embodiments, at least a portion of the epitope with which the inventive antibodies and antigen-binding fragments thereof interacts comprises the loop connecting α6 to α7 of PreF and/or β6 of PreF. In certain embodiments, the heavy chain (e.g., CDRL3) and the light chain (e.g., CDRH2) of the inventive antibodies interact with the epitope of PreF. In a particular embodiment, Tyr33 in CDRL1 and Tyr93 in CDRL3 both contact the α6-α7 loop of RSV preF and/or five consecutive serine residues, preferably followed by a tyrosine residue (Tyr56), in CDRH2 form a network of hydrogen bonds with Asp310 on β6 of RSV preF. In still further embodiments, the CDRH3 of the inventive antibodies have relatively few sequence (composition and/or length) restrictions.

In certain embodiments, the inventive antibodies and antigen-binding fragments thereof display an in vitro neutralization potency (IC 50 ) of greater than 0.5 ug/ml (referred to as “weak neutralization potency”); between about 0.5 ug/ml to about 5 ug/ml (referred to as “low neutralization potency”); between about 0.05 ug/ml to about 0.5 ug/ml (referred to as “medium neutralization potency”); or less than about 0.05 mg/ml (referred to as “high neutralization potency”). Neutralization potency can be measured using standard assays well known in the field, including, but not limited to, a high-throughput fluorescence plate reader neutralization assay (as described herein, see EXAMPLES).

In certain embodiments, the inventive antibodies and antigen-binding fragments thereof display at least about 2-fold; at least about 3-fold; at least about 4-fold; at least about 5-fold; at least about 6-fold; at least about 7-fold; at least about 8-fold; at least about 9-fold; at least about 10-fold; at least about 15-fold; at least about 20-fold; at least about 25-fold; at least about 30-fold; at least about 35-fold; at least about 40-fold; at least about 50-fold; at least about 55-fold; at least about 60-fold; at least about 70-fold; at least about 80-fold; at least about 90-fold; at least about 100-fold; greater than about 100-fold; and folds in between any of the foregoing; greater neutralization potency (IC 50 ) than motavizumab, MPE8, and D25.

In certain embodiments, the inventive antibodies and antigen-binding fragments thereof comprise the CDRH3 amino acid sequence of any one of the antibodies designated Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

In certain embodiments, the inventive antibodies and antigen-binding fragments thereof comprise the CDRH2 amino acid sequence of any one of the antibodies designated Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

In certain embodiments, the inventive antibodies and antigen-binding fragments thereof comprise the CDRH1 amino acid sequence of any one of the antibodies designated Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

In certain embodiments, the inventive antibodies and antigen-binding fragments thereof comprise the CDRL3 amino acid sequence of any one of the antibodies designated Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

In certain embodiments, the inventive antibodies and antigen-binding fragments thereof comprise the CDRL2 amino acid sequence of any one of the antibodies designated Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

In certain embodiments, the inventive antibodies and antigen-binding fragments thereof comprise the CDRL1 amino acid sequence of any one of the antibodies designated Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

In certain embodiments, the inventive antibodies and antigen-binding fragments thereof comprise any combination of two or more of the CDRH3, CDRH2, CDRH1, CDRL3, CDRL2, and CDRL1 amino acid sequences of any one of the antibodies designated Antibody Number 1 through Antibody Number 947 as disclosed in Table 5. By way of example only, the inventive antibodies and antigen-binding fragments thereof comprise the CDRL3 and the CDRH2 of any one of the antibodies designated Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

In certain embodiments, the inventive antibodies and antigen-binding fragments thereof comprise a heavy chain (HC) amino acid sequence of any one of the antibodies designated Antibody Number 1 through Antibody Number 947 as disclosed in Table 5. In certain embodiments, the inventive antibodies and antigen-binding fragments thereof comprise a light chain (LC) amino acid sequence of any one of the antibodies designated Antibody Number 1 through Antibody Number 947 as disclosed in Table 5. In certain embodiments, the inventive antibodies and antigen-binding fragments thereof comprise a heavy chain (HC) amino acid sequence and a light chain (LC) amino acid sequence of any one of the antibodies designated Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

In certain embodiments, the inventive antibodies and antigen-binding fragments thereof are each selected from the group consisting antibodies that are at least 70% identical; at least 75% identical; 80% identical; at least 85% identical; at least 90% identical; at least 95% identical; at least 96% identical; at least 97% identical; at least 98% identical; at least 99%; and/or all percentages of identity in between; to any one of the antibodies designated as Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

In certain embodiments, the inventive antibodies and antigen-binding fragments thereof comprise are each selected from the group consisting of the antibodies designated as Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

In certain embodiments, isolated nucleic acid sequences are provided that encode antibodies (or antigen-binding fragments thereof) that specifically bind to RSV F, wherein at least one of the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and/or CDRL3 amino acid sequences of the antibody or the antigen-binding fragment thereof is at least 70% identical; at least 75% identical; 80% identical; at least 85% identical; at least 90% identical; at least 95% identical; at least 96% identical; at least 97% identical; at least 98% identical; at least 99%; and/or all percentages of identity in between; to at least one of the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and/or CDRL3 amino acid sequences of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5. In certain embodiments, such nucleic acid sequences are selected from those nucleic acid sequences that are disclosed in Table 5 and compliments thereof.

In certain embodiments, isolated nucleic acid sequences are provided that encode the inventive antibodies and antigen-binding fragments thereof, wherein such nucleic acid sequences comprise sequences that encode the CDRH3 amino acid sequence of the antibodies designated Antibody Number 1 through Antibody Number 947 as disclosed in Table 5. In certain embodiments, such nucleic acid sequences are selected from those nucleic acid sequences that are disclosed in Table 5 and compliments thereof.

In certain embodiments, isolated nucleic acid sequences are provided that encode the inventive antibodies and antigen-binding fragments thereof, wherein such nucleic acid sequences comprise sequences that encode the CDRH2 amino acid sequences of the antibodies designated Antibody Number 1 through Antibody Number 947 as disclosed in Table 5. In certain embodiments, such nucleic acid sequences are selected from those nucleic acid sequences that are disclosed in Table 5 and compliments thereof.

In certain embodiments, isolated nucleic acid sequences are provided that encode the inventive antibodies and antigen-binding fragments thereof, wherein such nucleic acid sequences comprise sequences that encode the CDRH1 amino acid sequences of the antibodies designated Antibody Number 1 through Antibody Number 947 as disclosed in Table 5. In certain embodiments, such nucleic acid sequences are selected from those nucleic acid sequences that are disclosed in Table 5 and compliments thereof.

In certain embodiments, isolated nucleic acid sequences are provided that encode the inventive antibodies and antigen-binding fragments thereof, wherein such nucleic acid sequences comprise sequences that encode the CDRL3 amino acid sequences of the antibodies designated Antibody Number 1 through Antibody Number 947 as disclosed in Table 5. In certain embodiments, such nucleic acid sequences are selected from those nucleic acid sequences that are disclosed in Table 5 and compliments thereof.

In certain embodiments, isolated nucleic acid sequences are provided that encode the inventive antibodies and antigen-binding fragments thereof, wherein such nucleic acid sequences comprise sequences that encode the CDRL2 amino acid sequences of the antibodies designated Antibody Number 1 through Antibody Number 947 as disclosed in Table 5. In certain embodiments, such nucleic acid sequences are selected from those nucleic acid sequences that are disclosed in Table 5 and compliments thereof.

In certain embodiments, isolated nucleic acid sequences are provided that encode the inventive antibodies and antigen-binding fragments thereof, wherein such nucleic acid sequences comprise sequences that encode the CDRL1 amino acid sequences of the antibodies designated Antibody Number 1 through Antibody Number 947 as disclosed in Table 5. In certain embodiments, such nucleic acid sequences are selected from those nucleic acid sequences that are disclosed in Table 5 and compliments thereof.

In certain embodiments, isolated nucleic acid sequences are provided that encode the inventive antibodies and antigen-binding fragments thereof, wherein such nucleic acid sequences comprise sequences that encode the heavy chain (HC) amino acid sequences of the antibodies designated Antibody Number 1 through Antibody Number 947 as disclosed in Table 5. In certain embodiments, such nucleic acid sequences are selected from those nucleic acid sequences that are disclosed in Table 5 and compliments thereof.

In certain embodiments, isolated nucleic acid sequences are provided that encode the inventive antibodies and antigen-binding fragments thereof, wherein such nucleic acid sequences comprise sequences that encode the light chain (LC) amino acid sequences of the antibodies designated Antibody Number 1 through Antibody Number 947 as disclosed in Table 5. In certain embodiments, such nucleic acid sequences are selected from those nucleic acid sequences that are disclosed in Table 5 and compliments thereof.

In certain embodiments, isolated nucleic acid sequences are provided that encode the inventive antibodies and antigen-binding fragments thereof, wherein such nucleic acid sequences comprise sequences that are each selected from the group consisting of sequences that are at least 70% identical; at least 75% identical; 80% identical; at least 85% identical; at least 90% identical; at least 95% identical; at least 96% identical; at least 97% identical; at least 98% identical; at least 99%; and/or all percentages of identity in between; to any one of the nucleic acid sequences that are disclosed in Table 5 and compliments thereof.

In certain embodiments, isolated nucleic acid sequences are provided that encode the inventive antibodies and antigen-binding fragments thereof, wherein such nucleic acid sequences comprise sequences selected from the nucleic acid sequences that are disclosed in Table 5 and compliments thereof.

In certain embodiments, expression vectors are provided comprising the isolated nucleic acid sequences disclosed herein. In some embodiments, a single expression vector comprises the isolated nucleic acid sequences (e.g., V H and V L , or HC and LC, are contained in the same vector). In this case, host cells are transfected, transformed, or transduced with a single expression vector. However, in other embodiments, more than one expression vector comprises the isolated nucleic acid sequences (e.g., V H and V L , or HC and LC, are each contained in a different vector). In this case, host cells are transfected, transformed, or transduced with more than one expression vector.

Host cells transfected, transformed, or transduced with the nucleic acid sequences and/or the expression vectors themselves are also encompassed by the subject invention.

Epitope Mapping and Related Technologies

As described above and as demonstrated in the EXAMPLES, Applicant has characterized inter alia the epitope binding of the inventive antibodies and antigen-binding fragments thereof. In addition to the methods utilized by Applicant, various other techniques are available to the skilled artisan that can be used to carry out such characterization or to otherwise ascertain whether an antibody “interacts with one or more amino acids” within a polypeptide or protein. Exemplary techniques include, for example, a routine cross-blocking assay such as that described Antibodies, Harlow and Lane (Cold Spring Harbor Press, Cold Spring Harb., N.Y.) can be performed. Other methods include alanine scanning mutational analysis, peptide blot analysis (Reineke (2004) Methods Mol Biol 248:443-63), peptide cleavage analysis crystallographic studies and NMR analysis. In addition, methods such as epitope excision, epitope extraction and chemical modification of antigens can be employed (Tomer (2000) Protein Science 9: 487-496). Another method that can be used to identify the amino acids within a polypeptide with which an antibody interacts is hydrogen/deuterium exchange detected by mass spectrometry. In general terms, the hydrogen/deuterium exchange method involves deuterium-labeling the protein of interest, followed by binding the antibody to the deuterium-labeled protein. Next, the protein/antibody complex is transferred to water and exchangeable protons within amino acids that are protected by the antibody complex undergo deuterium-to-hydrogen back-exchange at a slower rate than exchangeable protons within amino acids that are not part of the interface. As a result, amino acids that form part of the protein/antibody interface may retain deuterium and therefore exhibit relatively higher mass compared to amino acids not included in the interface. After dissociation of the antibody, the target protein is subjected to protease cleavage and mass spectrometry analysis, thereby revealing the deuterium-labeled residues that correspond to the specific amino acids with which the antibody interacts. See, e.g., Ehring (1999) Analytical Biochemistry 267 (2):252-259; Engen and Smith (2001) Anal. Chem. 73:256A-265A.

As the artisan will understand, an epitope can be formed both from contiguous amino acids or noncontiguous amino acids juxtaposed by tertiary folding of a protein. Epitopes formed from contiguous amino acids are typically retained on exposure to denaturing solvents, whereas epitopes formed by tertiary folding are typically lost on treatment with denaturing solvents. An epitope typically includes at least 3, and more usually, at least 5 or 8-10 amino acids in a unique spatial conformation.

Modification-Assisted Profiling (MAP), also known as Antigen Structure-based Antibody Profiling (ASAP) is a method that categorizes large numbers of monoclonal antibodies (mAbs) directed against the same antigen according to the similarities of the binding profile of each antibody to chemically or enzymatically modified antigen surfaces (see, e.g., US 2004/0101920). Each category may reflect a unique epitope either distinctly different from or partially overlapping with epitope represented by another category. This technology allows rapid filtering of genetically identical antibodies, such that characterization can be focused on genetically distinct antibodies. When applied to hybridoma screening, MAP may facilitate identification of rare hybridoma clones that produce mAbs having the desired characteristics. MAP may be used to sort the antibodies of the invention into groups of antibodies binding different epitopes.

As the artisan understands, one can easily determine whether an antibody binds to the same epitope as, or competes for binding with, a reference anti-RSV F antibody by using routine methods available in the art. For example, to determine if a test antibody binds to the same epitope as a reference RSV F antibody of the invention, the reference antibody is allowed to bind to a RSV F protein or peptide under saturating conditions. Next, the ability of a test antibody to bind to the RSV F molecule is assessed. If the test antibody is able to bind to RSV F following saturation binding with the reference anti-RSV F antibody, it can be concluded that the test antibody binds to a different epitope than the reference anti-RSV F antibody. On the other hand, if the test antibody is not able to bind to the RSV F molecule following saturation binding with the reference anti-RSV F antibody, then the test antibody may bind to the same epitope as the epitope bound by the reference anti-RSV F antibody of the invention.

To determine if an antibody competes for binding with a reference anti-RSV F antibody, the above-described binding methodology is performed in two orientations. In a first orientation, the reference antibody is allowed to bind to a RSV F molecule under saturating conditions followed by assessment of binding of the test antibody to the RSV F molecule. In a second orientation, the test antibody is allowed to bind to a RSV F molecule under saturating conditions followed by assessment of binding of the reference antibody to the RSV F molecule. If, in both orientations, only the first (saturating) antibody is capable of binding to the RSV F molecule, then it is concluded that the test antibody and the reference antibody compete for binding to RSV F. As will be appreciated by a person of ordinary skill in the art, an antibody that competes for binding with a reference antibody may not necessarily bind to the identical epitope as the reference antibody, but may sterically block binding of the reference antibody by binding an overlapping or adjacent epitope.

Two antibodies bind to the same or overlapping epitope if each competitively inhibits (blocks) binding of the other to the antigen. That is, a 1-, 5-, 10-, 20-, or 100-fold excess of one antibody inhibits binding of the other by at least 50% but preferably 75%, 90% or even 99% as measured in a competitive binding assay (see, e.g., Junghans et al., Cancer Res. (1990) 50:1495-1502). Alternatively, two antibodies have the same epitope if essentially all amino acid mutations in the antigen that reduce or eliminate binding of one antibody reduce or eliminate binding of the other. Two antibodies have overlapping epitopes if some amino acid mutations that reduce or eliminate binding of one antibody reduce or eliminate binding of the other.

Additional routine experimentation (e.g., peptide mutation and binding analyses) can then be carried out to confirm whether the observed lack of binding of the test antibody is in fact due to binding to the same epitope as the reference antibody or if steric blocking (or another phenomenon) is responsible for the lack of observed binding. Experiments of this sort can be performed using ELISA, RIA, surface plasmon resonance, flow cytometry or any other quantitative or qualitative antibody-binding assay available in the art.

Immunoconjugates

The invention encompasses a RSV F antibody conjugated to a therapeutic moiety (“immunoconjugate”), such as an agent that is capable of reducing the severity of primary infection with RSV, or ameliorating at least one symptom associated with RSV infection, including coughing, fever, pneumonia, or the severity thereof. Such an agent may be a second different antibody to RSVF or a vaccine. The type of therapeutic moiety that may be conjugated to the anti-RSV F antibody and will take into account the condition to be treated and the desired therapeutic effect to be achieved. Alternatively, if the desired therapeutic effect is to treat the sequelae or symptoms associated with RSV infection, or any other condition resulting from such infection, such as, but not limited to, pneumonia, it may be advantageous to conjugate an agent appropriate to treat the sequelae or symptoms of the condition, or to alleviate any side effects of the antibodies of the invention. Examples of suitable agents for forming immunoconjugates are known in the art, see for example, WO 05/103081.

Multi-specific Antibodies

The antibodies of the present invention may be mono-specific, bi-specific, or multi-specific. Multi-specific antibodies may be specific for different epitopes of one target polypeptide or may contain antigen-binding domains specific for more than one target polypeptide. See, e.g., Tutt et al., 1991, J. Immunol. 147:60-69; Kufer et al., 2004, Trends Biotechnol. 22:238-244. As discussed above, the antibodies of the present invention can be linked to or co-expressed with another functional molecule, e.g., another peptide or protein. For example, an antibody or fragment thereof can be functionally linked (e.g., by chemical coupling, genetic fusion, noncovalent association or otherwise) to one or more other molecular entities, such as another antibody or antibody fragment to produce a bi-specific or a multi-specific antibody with a second binding specificity.

An exemplary bi-specific antibody format that can be used in the context of the present invention involves the use of a first immunoglobulin (Ig) C H 3 domain and a second Ig C H 3 domain, wherein the first and second Ig C H 3 domains differ from one another by at least one amino acid, and wherein at least one amino acid difference reduces binding of the bi-specific antibody to Protein A as compared to a bi-specific antibody lacking the amino acid difference. In one embodiment, the first Ig C H 3 domain binds Protein A and the second Ig C H 3 domain contains a mutation that reduces or abolishes Protein A binding such as an H95R modification (by IMGT exon numbering; H435R by EU numbering). The second C H 3 may further comprise a Y96F modification (by IMGT; Y436F by EU). Further modifications that may be found within the second C H 3 include: D16E, L18M, N44S, K52N, V57M, and V82I (by IMGT; D356E, L358M, N384S, K392N, V397M, and V422I by EU) in the case of lgG1 antibodies; N44S, K52N, and V82I (IMGT; N384S, K392N, and V422I by EU) in the case of lgG2 antibodies; and Q15R, N44S, K52N, V57M, R69K, E79Q, and V82I (by IMGT; Q355R, N384S, K392N, V397M, R409K, E419Q, and V422I by EU) in the case of lgG4 antibodies. Variations on the bi-specific antibody format described above are contemplated within the scope of the present invention.

Therapeutic Administration and Formulations

The invention provides therapeutic compositions comprising the inventive anti-RSV F antibodies or antigen-binding fragments thereof. The administration of therapeutic compositions in accordance with the invention will be administered with suitable carriers, excipients, and other agents that are incorporated into formulations to provide improved transfer, delivery, tolerance, and the like. A multitude of appropriate formulations can be found in the formulary known to all pharmaceutical chemists: Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, Pa. These formulations include, for example, powders, pastes, ointments, jellies, waxes, oils, lipids, lipid (cationic or anionic) containing vesicles (such as LIPOFECTIN™), DNA conjugates, anhydrous absorption pastes, oil-in-water and water-in-oil emulsions, emulsions carbowax (polyethylene glycols of various molecular weights), semi-solid gels, and semi-solid mixtures containing carbowax. See also Powell et al. “Compendium of excipients for parenteral formulations” PDA (1998) J Pharm Sci Technol 52:238-311.

The dose of each of the antibodies of the invention may vary depending upon the age and the size of a subject to be administered, target disease, conditions, route of administration, and the like. When the antibodies of the present invention are used for treating a RSV infection in a patient, or for treating one or more symptoms associated with a RSV infection, such as the cough or pneumonia associated with a RSV infection in a patient, or for lessening the severity of the disease, it is advantageous to administer each of the antibodies of the present invention intravenously or subcutaneously normally at a single dose of about 0.01 to about 30 mg/kg body weight, more preferably about 0.1 to about 20 mg/kg body weight, or about 0.1 to about 15 mg/kg body weight, or about 0.02 to about 7 mg/kg body weight, about 0.03 to about 5 mg/kg body weight, or about 0.05 to about 3 mg/kg body weight, or about 1 mg/kg body weight, or about 3.0 mg/kg body weight, or about 10 mg/kg body weight, or about 20 mg/kg body weight. Multiple doses may be administered as necessary. Depending on the severity of the condition, the frequency and the duration of the treatment can be adjusted. In certain embodiments, the antibodies or antigen-binding fragments thereof of the invention can be administered as an initial dose of at least about 0.1 mg to about 800 mg, about 1 to about 600 mg, about 5 to about 300 mg, or about 10 to about 150 mg, to about 100 mg, or to about 50 mg. In certain embodiments, the initial dose may be followed by administration of a second or a plurality of subsequent doses of the antibodies or antigen-binding fragments thereof in an amount that can be approximately the same or less than that of the initial dose, wherein the subsequent doses are separated by at least 1 day to 3 days; at least one week, at least 2 weeks; at least 3 weeks; at least 4 weeks; at least 5 weeks; at least 6 weeks; at least 7 weeks; at least 8 weeks; at least 9 weeks; at least 10 weeks; at least 12 weeks; or at least 14 weeks.

Various delivery systems are known and can be used to administer the pharmaceutical composition of the invention, e.g., encapsulation in liposomes, microparticles, microcapsules, recombinant cells capable of expressing the mutant viruses, receptor mediated endocytosis (see, e.g., Wu et al. (1987) J. Biol. Chem. 262:4429-4432). Methods of introduction include, but are not limited to, intradermal, transdermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural and oral routes. The composition may be administered by any convenient route, for example by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings {e.g., oral mucosa, nasal mucosa, rectal and intestinal mucosa, etc.) and may be administered together with other biologically active agents. Administration can be systemic or local. It may be delivered as an aerosolized formulation (See U.S. Publication No. 2011/0311515 and U.S. Publication No. 2012/0128669). The delivery of agents useful for treating respiratory diseases by inhalation is becoming more widely accepted (See A. J. Bitonti and J. A. Dumont, (2006), Adv. Drug Deliv. Rev, 58:1 106-1 1 18). In addition to being effective at treating local pulmonary disease, such a delivery mechanism may also be useful for systemic delivery of antibodies (See Maillet et al. (2008), Pharmaceutical Research, Vol. 25, No. 6, 2008).

The pharmaceutical composition can be also delivered in a vesicle, in particular a liposome (see, for example, Langer (1990) Science 249:1527-1533).

In certain situations, the pharmaceutical composition can be delivered in a controlled release system. In one embodiment, a pump may be used. In another embodiment, polymeric materials can be used. In yet another embodiment, a controlled release system can be placed in proximity of the composition's target, thus requiring only a fraction of the systemic dose.

The injectable preparations may include dosage forms for intravenous, subcutaneous, intracutaneous and intramuscular injections, drip infusions, etc. These injectable preparations may be prepared by methods publicly known. For example, the injectable preparations may be prepared, e.g., by dissolving, suspending or emulsifying the antibody or its salt described above in a sterile aqueous medium or an oily medium conventionally used for injections. As the aqueous medium for injections, there are, for example, physiological saline, an isotonic solution containing glucose and other auxiliary agents, etc., which may be used in combination with an appropriate solubilizing agent such as an alcohol (e.g., ethanol), a polyalcohol (e.g., propylene glycol, polyethylene glycol), a nonionic surfactant [e.g., polysorbate 80, HCO-50 (polyoxyethylene (50 mol) adduct of hydrogenated castor oil)], etc. As the oily medium, there are employed, e.g., sesame oil, soybean oil, etc., which may be used in combination with a solubilizing agent such as benzyl benzoate, benzyl alcohol, etc. The injection thus prepared is preferably filled in an appropriate ampoule.

A pharmaceutical composition of the present invention can be delivered subcutaneously or intravenously with a standard needle and syringe. In addition, with respect to subcutaneous delivery, a pen delivery device readily has applications in delivering a pharmaceutical composition of the present invention. Such a pen delivery device can be reusable or disposable. A reusable pen delivery device generally utilizes a replaceable cartridge that contains a pharmaceutical composition. Once all of the pharmaceutical composition within the cartridge has been administered and the cartridge is empty, the empty cartridge can readily be discarded and replaced with a new cartridge that contains the pharmaceutical composition. The pen delivery device can then be reused. In a disposable pen delivery device, there is no replaceable cartridge. Rather, the disposable pen delivery device comes prefilled with the pharmaceutical composition held in a reservoir within the device. Once the reservoir is emptied of the pharmaceutical composition, the entire device is discarded.

Numerous reusable pen and autoinjector delivery devices have applications in the subcutaneous delivery of a pharmaceutical composition of the present invention. Examples include, but certainly are not limited to AUTOPEN™ (Owen Mumford, Inc., Woodstock, UK), DISETRONIC™ pen (Disetronic Medical Systems, Burghdorf, Switzerland), HUMALOG MIX 75/25™ pen, HUMALOG™ pen, HUMALIN 70/30™ pen (Eli Lilly and Co., Indianapolis, Ind.), NOVOPEN™ I, II and III (Novo Nordisk, Copenhagen, Denmark), NOVOPEN JUNIOR™ (Novo Nordisk, Copenhagen, Denmark), BD™ pen (Becton Dickinson, Franklin Lakes, N.J.), OPTIPEN™, OPTIPEN PRO™ OPTIPEN STARLET™, and OPTICLIK™ (sanofi-aventis, Frankfurt, Germany), to name only a few. Examples of disposable pen delivery devices having applications in subcutaneous delivery of a pharmaceutical composition of the present invention include, but certainly are not limited to the SOLOSTAR™ pen (sanofi-aventis), the FLEXPEN™ (Novo Nordisk), and the KWIKPEN™ (Eli Lilly), the SURECLICK™ Autoinjector (Amgen, Thousands Oaks, Calif.), the PENLET™ (Haselmeier, Stuttgart, Germany), the EPIPEN (Dey, L.P.) and the HUMIRA™ Pen (Abbott Labs, Abbott Park, Ill.), to name only a few.

Advantageously, the pharmaceutical compositions for oral or parenteral use described above are prepared into dosage forms in a unit dose suited to fit a dose of the active ingredients. Such dosage forms in a unit dose include, for example, tablets, pills, capsules, injections (ampoules), suppositories, etc. The amount of the aforesaid antibody contained is generally about 5 to about 500 mg per dosage form in a unit dose; especially in the form of injection, it is preferred that the aforesaid antibody is contained in about 5 to about 100 mg and in about 10 to about 250 mg for the other dosage forms.

Administration Regimens

According to certain embodiments, multiple doses of an antibody to RSV F may be administered to a subject over a defined time course. The methods according to this aspect of the invention comprise sequentially administering to a subject multiple doses of an antibody to RSV F. As used herein, “sequentially administering” means that each dose of antibody to RSV F is administered to the subject at a different point in time, e.g., on different days separated by a predetermined interval (e.g., hours, days, weeks or months). The present invention includes methods which comprise sequentially administering to the patient a single initial dose of an antibody to RSV F, followed by one or more secondary doses of the antibody to RSV F and, optionally, followed by one or more tertiary doses of the antibody to RSV F.

The terms “initial dose,” “secondary doses,” and “tertiary doses,” refer to the temporal sequence of administration of the antibody to RSV F. Thus, the “initial dose” is the dose which is administered at the beginning of the treatment regimen (also referred to as the “baseline dose”); the “secondary doses” are the doses which are administered after the initial dose; and the “tertiary doses” are the doses which are administered after the secondary doses. The initial, secondary, and tertiary doses may all contain the same amount of antibody to RSV F, but generally may differ from one another in terms of frequency of administration. In certain embodiments, however, the amount of antibody to RSV F contained in the initial, secondary and/or tertiary doses vary from one another (e.g., adjusted up or down as appropriate) during the course of treatment. In certain embodiments, two or more (e.g., 2, 3, 4, or 5) doses are administered at the beginning of the treatment regimen as “loading doses” followed by subsequent doses that are administered on a less frequent basis (e.g., “maintenance doses”).

In one exemplary embodiment of the present invention, each secondary and/or tertiary dose is administered 1 to 26 (e.g., 1, 1½, 2, 2½, 3, 3½, 4, 4½, 5, 5½, 6, 6½, 7, 7½, 8, 8½, 9, 9½, 10, 10½, 11, 11½, 12, 12½, 13, 13½, 14, 14½, 15, 15½, 16, 16½, 17, 17½, 18, 18½, 19, 19½, 20, 20½, 21, 21 ½, 22, 22½, 23, 23½, 24, 24½, 25, 25½, 26, 26½, or more) weeks after the immediately preceding dose. The phrase “the immediately preceding dose,” as used herein, means that in a sequence of multiple administrations, the dose of antibody to RSV F, which is administered to a patient prior to the administration of the very next dose in the sequence with no intervening doses.

The methods according to this aspect of the invention may comprise administering to a patient any number of secondary and/or tertiary doses of an antibody to RSV F. For example, in certain embodiments, only a single secondary dose is administered to the patient. In other embodiments, two or more (e.g., 2, 3, 4, 5, 6, 7, 8, or more) secondary doses are administered to the patient. Likewise, in certain embodiments, only a single tertiary dose is administered to the patient. In other embodiments, two or more (e.g., 2, 3, 4, 5, 6, 7, 8, or more) tertiary doses are administered to the patient.

In embodiments involving multiple secondary doses, each secondary dose may be administered at the same frequency as the other secondary doses. For example, each secondary dose may be administered to the patient 1 to 2 weeks after the immediately preceding dose. Similarly, in embodiments involving multiple tertiary doses, each tertiary dose may be administered at the same frequency as the other tertiary doses. For example, each tertiary dose may be administered to the patient 2 to 4 weeks after the immediately preceding dose. Alternatively, the frequency at which the secondary and/or tertiary doses are administered to a patient can vary over the course of the treatment regimen. The frequency of administration may also be adjusted during the course of treatment by a physician depending on the needs of the individual patient following clinical examination.

Accordingly, in certain embodiments are provided pharmaceutical compositions comprising: one or more of the inventive antibodies or antigen-binding fragments thereof disclosed herein and throughout and a pharmaceutically acceptable carrier and/or one or more excipients. In certain other embodiments are provided pharmaceutical compositions comprising: one or more nucleic acid sequences encoding one or more inventive antibodies or antigen-binding fragments thereof; or one or more the expression vectors harbouring such nucleic acid sequences; and a pharmaceutically acceptable carrier and/or one or more excipients.

Therapeutic Uses of the Antibodies

Due to their binding to and interaction with RSV F, it is believed that the inventive antibodies and antigen-binding fragments thereof are useful for preventing fusion of the virus with the host cell membrane, preventing cell to cell virus spread, and/or inhibiting syncytia formation. Additionally, a subset of the inventive anti-RSV antibodies and antigen-binding fragments thereof display specificity for RSV (i.e., epitopic specificity) that is unique from the specificity of adult anti-RSV antibodies. Therefore, the inventive antibodies and antigen-binding fragments thereof may be advantageous for preventing and/or treating an RSV infection in an infant. As such, the antibodies of the invention are contemplated for prophylactic use in infant, particularly pre-term infants and full-term infants born during RSV season (late fall to early spring). It is contemplated that the antibodies of the invention may be used alone, or in conjunction with one or more additional agents, for treating or preventing RSV infection or at least one symptom or complication associated with RSV infection. The second or third agents may be delivered concurrently with or separately (before or after) from the antibodies of the invention. The one or more additional agents may be an anti-viral (e.g., ribavirin), an NSAID or other agents to reduce fever or pain, another antibody that specifically binds RSV-F, an agent (e.g. an antibody) that binds to another RSV antigen (e.g., RSV G), a vaccine against RSV, and/or an siRNA specific for an RSV antigen.

In yet a further embodiment of the invention, the present antibodies are used for the preparation of a pharmaceutical composition for treating patients suffering from a RSV infection. The pharmaceutical composition can reduce the severity of a primary infection with RSV, reduce the duration of the infection, and/or reduce at least one symptom associated with the RSV infection. In a further embodiment, the anti-RSV F antibodies disclosed herein are used as adjunct therapy with any other agent useful for treating an RSV infection, including an antiviral, a toxoid, a vaccine, a second RSV-F antibody, or another antibody specific for an RSV antigen, including an RSV-G antibody, or any other palliative therapy known to those skilled in the art.

Accordingly, the disclosure provides methods of treating or preventing RSV infection, or at least one symptom associated with RSV infection, comprising administering to a patient in need thereof (or suspected of being in need thereof) one or more of the inventive antibodies or antigen-binding fragments thereof, e.g., one or more of the anti-RSV F antibodies disclosed in Table 5, such that the RSV infection is treated or prevented, or the at least on symptom associated with RSV infection is treated, alleviated, or reduced in severity.

Other embodiments provide methods of treating or preventing a RSV infection, or at least one symptom associated with RSV infection, comprising administering to a patient in need thereof (or suspected of being in need thereof) a nucleic acid sequence encoding one or more of the inventive antibodies or antigen-binding fragments thereof, such nucleic acid sequenced disclosed in Table 5 and compliments thereof, such that the RSV infection is treated or prevented, or the at least on symptom associated with RSV infection is treated, alleviated, or reduced in severity.

Additional embodiments provide methods of treating or preventing a RSV infection, or at least one symptom associated with RSV infection, comprising administering to a patient in need thereof (or suspected of being in need thereof) a host cell harboring a nucleic acid sequence or an expression vector comprising such a nucleic acid sequence, wherein such nucleic acid sequences is selected from the group consisting of sequences disclosed in Table 5 and compliments thereof, such that the RSV infection is treated or prevented, or the at least one symptom associated with RSV infection is treated, alleviated, or reduced in severity.

Further embodiments provide methods of treating or preventing a RSV infection, or at least one symptom associated with RSV infection, comprising administering to a patient in need thereof (or suspected of being in need thereof) a pharmaceutical composition comprising one or more of the inventive antibodies or antigen-binding fragments thereof as disclosed in Table 5, or one or more nucleic acid sequences or an expression vectors comprising such a nucleic acid sequence, wherein such nucleic acid sequences are selected from the group consisting of sequences disclosed in Table 5 and compliments thereof; one or more host cells harboring one or more nucleic acid sequences or an expression vectors comprising such one or more nucleic acid sequences, wherein such nucleic acid sequences are selected from the group consisting of sequences disclosed in Table 5 and compliments thereof; and a pharmaceutically acceptable carrier and/or one or more excipients, such that the RSV infection is treated or prevented, or the at least on symptom associated with RSV infection is treated, alleviated, or reduced in severity.

The anti-RSV F antibodies disclosed herein may also be suitable for therapeutic and/or prophylactic use in non-humans, e.g., cattle, swine, sheep, or poultry.

Combination Therapies

As noted above, according to certain embodiments, the disclosed methods comprise administering to the subject one or more additional therapeutic agents in combination with an antibody to RSV F. As used herein, the expression “in combination with” means that the additional therapeutic agents are administered before, after, or concurrent with the pharmaceutical composition comprising the anti-RSV F antibody. The term “in combination with” also includes sequential or concomitant administration of the anti-RSV F antibody and a second therapeutic agent.

For example, when administered “before” the pharmaceutical composition comprising the anti-RSV F antibody, the additional therapeutic agent may be administered about 72 hours, about 60 hours, about 48 hours, about 36 hours, about 24 hours, about 12 hours, about 10 hours, about 8 hours, about 6 hours, about 4 hours, about 2 hours, about 1 hour, about 30 minutes, about 15 minutes or about 10 minutes prior to the administration of the pharmaceutical composition comprising the anti-RSV F antibody. When administered “after” the pharmaceutical composition comprising the anti-RSV-F antibody, the additional therapeutic agent may be administered about 10 minutes, about 15 minutes, about 30 minutes, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 12 hours, about 24 hours, about 36 hours, about 48 hours, about 60 hours or about 72 hours after the administration of the pharmaceutical composition comprising the anti-RSV F antibodies. Administration “concurrent” or with the pharmaceutical composition comprising the anti-RSV F antibody means that the additional therapeutic agent is administered to the subject in a separate dosage form within less than 5 minutes (before, after, or at the same time) of administration of the pharmaceutical composition comprising the anti-RSV F antibody, or administered to the subject as a single combined dosage formulation comprising both the additional therapeutic agent and the anti-RSV F antibody.

Combination therapies may include an anti-RSV F antibody of the invention and any additional therapeutic agent that may be advantageously combined with an antibody of the invention, or with a biologically active fragment of an antibody of the invention.

For example, a second or third therapeutic agent may be employed to aid in reducing the viral load in the lungs, such as an antiviral, for example, ribavirin. The antibodies may also be used in conjunction with other therapies, as noted above, including a toxoid, a vaccine specific for RSV, a second antibody specific for RSV F, or an antibody specific for another RSV antigen, such as RSV G.

Diagnostic Uses of the Antibodies

The inventive anti-RSV antibodies and antigen-binding fragments thereof may also be used to detect and/or measure RSV in a sample, e.g., for diagnostic purposes. It is envisioned that confirmation of an infection thought to be caused by RSV may be made by measuring the presence of the virus through use of any one or more of the antibodies of the invention. Exemplary diagnostic assays for RSV may comprise, e.g., contacting a sample, obtained from a patient, with an anti-RSV F antibody of the invention, wherein the anti-RSV F antibody is labeled with a detectable label or reporter molecule or used as a capture ligand to selectively isolate the virus containing the F protein from patient samples. Alternatively, an unlabeled anti-RSV F antibody can be used in diagnostic applications in combination with a secondary antibody which is itself detectably labeled. The detectable label or reporter molecule can be a radioisotope, such as 3 H, 14 C, 32 P 35 S, or 125 I; a fluorescent or chemiluminescent moiety such as fluorescein isothiocyanate, or rhodamine; or an enzyme such as alkaline phosphatase, β-galactosidase, horseradish peroxidase, or luciferase. Specific exemplary assays that can be used to detect or measure RSV containing the F protein in a sample include enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (MA), and fluorescence-activated cell sorting (FACS).

Samples that can be used in RSV diagnostic assays according to the present invention include any tissue or fluid sample obtainable from a patient, which contains detectable quantities of RSV F protein, or fragments thereof, under normal or pathological conditions. Generally, levels of RSV F in a particular sample obtained from a healthy patient (e.g., a patient not afflicted with a disease or condition associated with the presence of RSV F) will be measured to initially establish a baseline, or standard, level of the F protein from RSV. This baseline level of RSV F can then be compared against the levels of RSV F measured in samples obtained from individuals suspected of having an RSV infection or symptoms associated with such infection.

EXAMPLES

Example 1. Isolation and Characterization of Anti-RSV F-Specific Human Infant Antibodies from Memory B Cells

Applicant has comprehensively profiled the human infant antibody response to RSV F by isolating and characterizing over 450 RSV F-specific monoclonal antibodies from the memory B cells of RSV-infected infants, and used these antibodies to characterize the infant antibody response as well as develop a framework for the rational design of age-specific RSV vaccines. The antibody responses were highly biased, with half of the antibodies recognizing only two antigenic sites. Antibodies targeting both sites showed convergent sequence features, the molecular determinants of which were revealed by X-ray crystallographic studies. A subset of antibodies targeting one of the sites displayed potent neutralizing activity despite lacking somatic mutations, suggesting suitably designed vaccines may be used to induce such antibodies in young infants.

RSV F-Specific Antibodies Isolated from Young Infants have Low Levels of SHM and Biased V H and V L Germline Gene Usage

To analyze infant B cell responses to RSV F, blood samples from seven infants that were hospitalized due to complications associated with RSV infection were obtained. Of the seven infants, five were less than three months (<3 mo.) and two were at least six months (>6 mo.) of age at the time of hospitalization (Table 1). Blood was drawn from seven infants hospitalized with bronchiolitis and confirmed RSV infection.

TABLE 1

Clinical information for infant donors

Estimated Age at

gestational Birth Hospital Intensity admission Age at blood

ID age (weeks) weight (kg) stay (days) of care a Intubation (months) draw (months)

2308 39 3.29 5 R N 0.35 1.35

2026 37 2.41 7 I N 0.96 2.75

2301 40 4.5 4 R CPAP 1.48 3.00

2021 33 2.21 15 I N 1.61 4.46

2201 39 4.39 3 I N 2.54 12.35

856 32.5 2.07 3 I N 6.00 10.61

2042 38 3.29 1 I Y 26.64 29.57

a R, routine; I, intensive, all patients were administered O 2 .

Six out of the seven infants were infected during the first RSV season of their life and were therefore likely experiencing a primary infection. The remaining donor, who was 29.5 months old at the time of blood draw, was also likely experiencing a primary infection because secondary RSV infections generally do not result in hospitalization (Glezen et al., 1986). To assess the magnitude of the B cell response to RSV F, peripheral blood mononuclear cells (PBMCs) were stained with fluorescently labeled tetramers of preF and postF trimers and analyzed by flow cytometry ( FIGS. 1 A and 1 B ). The frequency of class-switched B cells that were RSV F-specific was substantially lower in infants <3 mo. compared with infants ≥6 mo. ( FIG. 1 C ). In infants <3 mo., the frequency of RSV F-specific class-switched B cells ranged from 0.05-0.3%, whereas in infants ≥6 mo. the frequency ranged from 1.2-1.6%. To dissect the RSV F-specific B cell response, between 100 and 300 RSV F-reactive B cells from each donor were single-cell sorted and the antibody variable heavy (VH)- and variable light (VL)-chain sequences were rescued by single-cell PCR (Tiller et al., 2008). Due to the low frequency of RSV F-specific class-switched B cells in the five younger infants, all B cells that reacted with RSV F were single-cell sorted ( FIG. 2 A ). For the two infants that were ≥6 mo., only class-switched B cells were sorted ( FIG. 2 B ). Although all B cells that reacted with RSV F were sorted from infants <3 mo., index sorting was performed in order to analyze the B cell surface markers expressed on each sorted cell. This analysis revealed that 14-60% of the RSV F-specific B cells sorted from infants <3 mo. were class-switched and/or CD27 + , with the remaining B cells lacking classical memory markers ( FIG. 2 C ), suggesting that RSV infection induces more robust B cell responses in infants ≥6 mo. compared with infants <3 mo.

In total, over 450 cognate VH and VL pairs were cloned and expressed as full-length IgGs in an engineered strain of Saccharomyces cerevisiae (Bornholdt et al., 2016; Swers et al., 2004). As expected, sequence analysis showed that the median level of SHM in class-switched B cells increased as a function of age ( FIG. 2 D ). Also, the majority of antibodies isolated from infants <3 mo. lacked SHM, similar to what was observed previously in postF-reactive B cells (Williams et al., 2009). However, nearly 5% of antibodies isolated from these infants had VH genes containing at least five nucleotide substitutions, consistent with previous studies showing that SHM does occur in young infants, albeit at relatively low frequency (Rechavi et al., 2015; Ridings et al., 1998). The level of SHM in antibodies isolated from the two infants ≥6 mo. was relatively high, with a median of 7 and 13 V H nucleotide substitutions resulting in a median of 6 and 11 amino acid substitutions, respectively ( FIG. 2 D ). Analysis of VH and VL germline gene usage showed that RSV F-reactive infant antibody responses were strongly biased toward either VH3-21/VL1-40 or the highly related VH3-11/VL1-40 gene pairing ( FIG. 2 E ). There was also a more modest preference for the VH1-18/VK2-30, VH1-18/VL3-21, and VH5-51/VL6-57 gene pairs ( FIG. 2 E ). The VH1-18/VK2-30 gene pair was present in 8.5% of RSV F-reactive antibodies isolated from adults and is associated with recognition of site V on prefusion F (Gilman et al., 2016; Mousa et al., 2017). Overall, the results demonstrate that RSV infection induced B cell responses with higher levels of SHM in infants ≥6 mo. compared to <3 mo., and that the responses in both age groups exhibit biased germline gene usage.

A Subset of Infant Antibodies Binds with High Affinity to RSV F and Potently Neutralizes RSV

To further characterize the infant antibodies, the apparent binding affinity of each antibody for preF and postF was determined. For each of the infants <3 mo., 24-34% of the isolated antibodies bound to preF with an apparent affinity of ≤5 nM, compared with 45% and 91% for the two infants ≥6 mo. ( FIG. 3 A ). Although a total of 40 such antibodies were isolated from the youngest three infants, only two antibodies with ≤5 nM affinity for postF were isolated from the same three infants ( FIG. 3 B ). In addition, for every infant the number of antibodies with ≤5 nM affinity for postF was lower than those with ≤5 nM affinity for preF ( FIG. 3 B ). Consistent with this result, the percentage of preF-specific antibodies ranged from 28-63%, whereas substantially smaller percentages (2-17%) were postF-specific ( FIG. 4 A ). Antibodies recognizing both preF and postF comprised about 19-36% of the antibody responses in the four oldest infants, but less than 10% of the response in the three youngest infants. Collectively, these results suggest that young infants generate a preF-biased antibody response that expands to include recognition of postF by six months of age.

Next, the antibodies were tested for neutralizing activity using a high-throughput assay. This analysis revealed that 12-49% of the antibodies isolated from each infant showed neutralizing activity, and a subset of antibodies isolated from six out of the seven infants showed highly potent neutralizing activity (IC 50 s<0.05 μg/ml) ( FIG. 3 C ). Interestingly, nearly 20% of the neutralizing antibodies lacked VH and VL gene mutations (Table 2), suggesting that extensive affinity maturation is not required for potent neutralization of RSV. The name, donor ID number, sequence information, binding affinity, neutralization IC 50 , epitope and index sort information for each antibody is shown in the table.

TABLE 2

Summary of antibody characteristics

Prefusion Postfusion Prefusion Postfusion Neut IC 50 Neut IC 50

subtype A subtype A subtype B subtype B (ug/ml) (ug/ml)

Name Donor K d (M)* K d (M)* K d (M)* K d (M)* subtype A* subtype B*

ADI-25462 Infant 2308 6.42E−10 N.B. 1.71E−09 N.B. 0.15 0.11

ADI-25467 Infant 2308 N.B. 2.53E−08 N.B. 2.62E−08 N.N. N.N.

ADI-25468 Infant 2308 2.89E−08 N.B. N.B. N.B. N.N. N.N.

ADI-25472 Infant 2308 1.19E−08 N.B. 3.77E−08 N.B. N.N. N.N.

ADI-25478 Infant 2308 2.43E−09 N.B. 6.43E−09 N.B. 2.18 3.52

ADI-25479 Infant 2308 1.57E−09 N.B. 4.29E−09 N.B. 0.24 0.29

ADI-25480 Infant 2308 1.27E−09 N.B. 4.27E−09 N.B. 0.17 0.17

ADI-25484 Infant 2308 3.79E−09 N.B. 1.84E−08 N.B. 15.28 8.58

ADI-25491 Infant 2308 3.74E−08 P.F. 2.19E−08 N.B. N.N. N.N.

ADI-25495 Infant 2308 8.70E−10 N.B. 6.41E−09 N.B. 0.24 5.60

ADI-25496 Infant 2308 2.08E−08 N.B. N.B. N.B. N.N. N.N.

ADI-25497 Infant 2308 5.00E−08 1.84E−08 1.41E−08 1.48E−08 N.N. N.N.

ADI-25502 Infant 2308 2.93E−08 P.F. N.B. N.B. N.N. N.N.

ADI-25503 Infant 2308 7.02E−09 N.B. N.B. N.B. N.N. N.N.

ADI-25505 Infant 2308 P.F. N.B. N.B. N.B. N.N. N.N.

ADI-25514 Infant 2308 4.45E−09 N.B. N.B. N.B. N.N. N.N.

ADI-25517 Infant 2308 N.B. P.F. N.B. N.B. N.N. N.N.

ADI-25518 Infant 2308 5.57E−08 P.F. 3.95E−08 N.B. N.N. N.N.

ADI-25524 Infant 2308 8.38E−09 N.B. 2.34E−08 N.B. 1.77 2.09

ADI-25532 Infant 2308 5.87E−10 N.B. 1.56E−09 N.B. 0.04 0.05

ADI-25533 Infant 2308 N.B. P.F. N.B. N.B. N.N. N.N.

ADI-25542 Infant 2308 9.05E−09 N.B. N.B. N.B. N.N. N.N.

ADI-25547 Infant 2308 N.B. 2.15E−08 2.03E−08 2.31E−08 N.N. N.N.

ADI-25548 Infant 2308 1.71E−08 N.B. N.B. N.B. N.N. N.N.

ADI-25549 Infant 2308 6.72E−09 N.B. 2.88E−08 N.B. 11.47 6.02

ADI-25555 Infant 2308 1.11E−08 N.B. 4.47E−08 N.B. 18.59 12.08

ADI-25556 Infant 2308 1.19E−08 N.B. 4.20E−08 N.B. N.N. N.N.

ADI-25557 Infant 2308 8.29E−09 N.B. 3.33E−08 N.B. N.N. N.N.

ADI-25559 Infant 2308 1.27E−08 N.B. 3.33E−08 N.B. N.N. N.N.

ADI-25562 Infant 2308 1.69E−09 N.B. 3.32E−09 N.B. 1.18 1.14

ADI-25565 Infant 2308 1.54E−08 N.B. 3.57E−08 N.B. N.N. N.N.

ADI-25567 Infant 2308 2.40E−09 N.B. 3.83E−09 N.B. 0.33 1.94

ADI-25569 Infant 2308 N.B. P.F. P.F. P.F. N.N. N.N.

ADI-25572 Infant 2308 N.B. N.B. P.F. P.F. N.N. N.N.

ADI-25573 Infant 2308 N.B. N.B. N.B. 4.86E−08 N.N. N.N.

ADI-25575 Infant 2308 N.B. N.B. N.B. 3.96E−08 5.64 N.N.

ADI-25576 Infant 2308 N.B. N.B. N.B. 2.39E−08 N.N. N.N.

ADI-25577 Infant 2308 1.40E−08 N.B. 4.42E−08 N.B. N.N. N.N.

ADI-25587 Infant 2308 N.B. 9.23E−09 N.B. 7.93E−09 N.N. N.N.

ADI-25588 Infant 2308 1.73E−08 N.B. N.B. N.B. N.N. N.N.

ADI-25595 Infant 2308 1.27E−08 N.B. N.B. N.B. N.N. N.N.

ADI-25598 Infant 2308 N.B. N.B. N.B. P.F. N.N. N.N.

ADI-19420 Infant 2026 5.70E−10 N.B. 2.47E−09 N.B. 0.55 0.64

ADI-19421 Infant 2026 7.22E−09 N.B. 5.42E−09 N.B. 10.00 3.30

ADI-19422 Infant 2026 2.23E−09 N.B. 1.08E−08 N.B. 0.73 1.90

ADI-19424 Infant 2026 1.07E−09 N.B. 1.71E−09 N.B. 0.08 0.21

ADI-19425 Infant 2026 4.56E−10 N.B. 1.37E−09 N.B. 0.02 0.04

ADI-19426 Infant 2026 2.87E−09 N.B. 1.29E−08 N.B. N.N. N.N.

ADI-19427 Infant 2026 2.78E−10 N.B. 5.00E−10 N.B. 0.01 0.03

ADI-19428 Infant 2026 4.96E−09 N.B. 1.67E−08 N.B. 3.25 N.N.

ADI-19429 Infant 2026 1.23E−08 N.B. N.B. N.B. N.N. N.N.

ADI-19430 Infant 2026 5.02E−09 N.B. 1.68E−08 N.B. N.N. N.N.

ADI-19431 Infant 2026 8.18E−09 N.B. 3.16E−09 N.B. 4.35 0.17

ADI-19432 Infant 2026 P.F. N.B. N.B. N.B. 10.98 N.N.

ADI-19433 Infant 2026 3.60E−09 N.B. N.B. N.B. 1.56 N.N.

ADI-19435 Infant 2026 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-19436 Infant 2026 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-19437 Infant 2026 N.B. P.F. N.B. N.B. N.N. N.N.

ADI-19439 Infant 2026 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-19440 Infant 2026 5.41E−09 N.B. 1.43E−08 N.B. N.N. N.N.

ADI-19441 Infant 2026 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-19444 Infant 2026 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-19445 Infant 2026 N.B. N.B. N.B. P.F. N.N. N.N.

ADI-19447 Infant 2026 P.F. N.B. N.B. N.B. N.N. N.N.

ADI-19448 Infant 2026 6.08E−09 N.B. 5.58E−09 N.B. 9.64 N.N.

ADI-19449 Infant 2026 1.48E−08 N.B. 2.60E−08 N.B. N.N. N.N.

ADI-19450 Infant 2026 N.B. N.B. 3.86E−08 N.B. N.N. N.N.

ADI-19454 Infant 2026 2.52E−09 N.B. 1.57E−08 N.B. N.N. N.N.

ADI-19455 Infant 2026 1.80E−08 N.B. N.B. N.B. N.N. N.N.

ADI-19457 Infant 2026 8.29E−09 N.B. 1.67E−08 N.B. N.N. N.N.

ADI-19458 Infant 2026 2.15E−10 N.B. 2.43E−10 N.B. 0.04 0.07

ADI-19459 Infant 2026 1.09E−09 N.B. 1.45E−09 N.B. 0.05 0.10

ADI-19460 Infant 2026 7.50E−09 N.B. 6.01E−09 N.B. N.N. N.N.

ADI-19461 Infant 2026 N.B. N.B. P.F. N.B. N.N. N.N.

ADI-19462 Infant 2026 N.B. P.F. N.B. N.B. N.N. N.N.

ADI-19463 Infant 2026 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-19465 Infant 2026 2.74E−09 N.B. 1.94E−08 N.B. N.N. N.N.

ADI-19506 Infant 2026 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-19507 Infant 2026 1.09E−08 N.B. 1.01E−08 N.B. N.N. N.N.

ADI-19509 Infant 2026 9.33E−09 N.B. 1.58E−09 N.B. 3.42 1.56

ADI-19510 Infant 2026 2.38E−10 N.B. 2.39E−10 N.B. 0.16 0.83

ADI-19511 Infant 2026 N.B. N.B. N.B. 1.53E−08 N.N. N.N.

ADI-24792 Infant 2301 6.52E−10 N.B. 1.83E−09 N.B. 0.27 0.19

ADI-24793 Infant 2301 N.B. N.B. N.B. 2.68E−08 N.N. N.N.

ADI-24795 Infant 2301 2.39E−08 N.B. 3.42E−08 N.B. N.N. N.N.

ADI-24796 Infant 2301 N.B. N.B. 8.22E−08 N.B. N.N. N.N.

ADI-24798 Infant 2301 9.92E−09 N.B. 5.27E−09 N.B. N.N. N.N.

ADI-24799 Infant 2301 1.22E−08 N.B. 1.90E−08 N.B. 11.53 N.N.

ADI-24800 Infant 2301 2.83E−08 N.B. 5.14E−08 N.B. N.N. N.N.

ADI-24801 Infant 2301 5.89E−08 N.B. N.B. N.B. N.N. N.N.

ADI-24803 Infant 2301 N.B. 1.20E−09 N.B. 4.42E−10 N.N. N.N.

ADI-24805 Infant 2301 3.79E−09 N.B. 4.88E−09 N.B. 0.21 0.71

ADI-24807 Infant 2301 N.B. 1.64E−08 N.B. N.B. N.N. N.N.

ADI-24808 Infant 2301 N.B. 1.08E−08 N.B. N.B. N.N. N.N.

ADI-24811 Infant 2301 8.10E−09 N.B. 4.29E−09 N.B. N.N. N.N.

ADI-24812 Infant 2301 3.51E−09 N.B. 7.58E−09 N.B. 0.18 N.N.

ADI-24813 Infant 2301 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-24814 Infant 2301 8.11E−09 N.B. 2.39E−09 N.B. 0.73 0.32

ADI-24815 Infant 2301 1.84E−08 N.B. 2.91E−08 N.B. N.N. N.N.

ADI-24816 Infant 2301 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-24817 Infant 2301 6.80E−09 N.B. 9.23E−09 N.B. 2.20 4.40

ADI-24818 Infant 2301 3.36E−08 6.47E−09 N.B. N.B. N.N. N.N.

ADI-24819 Infant 2301 6.52E−09 N.B. 9.44E−09 N.B. 4.33 6.28

ADI-24820 Infant 2301 3.06E−08 N.B. 3.85E−08 N.B. N.N. N.N.

ADI-24821 Infant 2301 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-24822 Infant 2301 4.65E−08 N.B. N.B. N.B. N.N. N.N.

ADI-24823 Infant 2301 4.16E−09 N.B. 6.03E−09 N.B. ND ND

ADI-24824 Infant 2301 1.51E−08 N.B. 4.75E−08 N.B. N.N. N.N.

ADI-24825 Infant 2301 3.31E−08 3.01E−08 N.B. 2.60E−08 N.N. N.N.

ADI-24826 Infant 2301 6.88E−09 N.B. 9.03E−09 N.B. N.N. N.N.

ADI-24827 Infant 2301 7.42E−09 N.B. 6.62E−09 N.B. 0.02 N.N.

ADI-24828 Infant 2301 3.06E−10 N.B. 3.91E−10 N.B. 0.02 0.04

ADI-24829 Infant 2301 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-24830 Infant 2301 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-24831 Infant 2301 4.88E−09 N.B. 6.23E−09 N.B. 0.21 3.29

ADI-24832 Infant 2301 1.80E−09 N.B. 1.95E−09 N.B. 0.49 0.24

ADI-24833 Infant 2301 1.93E−08 N.B. 1.14E−08 N.B. N.N. N.N.

ADI-24834 Infant 2301 1.12E−09 2.11E−10 7.32E−10 2.60E−10 N.N. N.N.

ADI-24835 Infant 2301 4.93E−09 N.B. 5.55E−09 N.B. 0.63 1.06

ADI-24836 Infant 2301 2.87E−09 N.B. 3.44E−09 N.B. N.N. N.N.

ADI-24837 Infant 2301 2.75E−08 N.B. N.B. N.B. N.N. N.N.

ADI-24838 Infant 2301 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-24839 Infant 2301 5.83E−09 N.B. 9.63E−09 N.B. 0.44 4.10

ADI-24840 Infant 2301 7.32E−09 N.B. 7.80E−09 N.B. N.N. N.N.

ADI-24841 Infant 2301 N.B. N.B. 2.66E−08 N.B. N.N. N.N.

ADI-24842 Infant 2301 5.59E−10 N.B. 2.76E−09 N.B. 0.03 0.03

ADI-24843 Infant 2301 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-24845 Infant 2301 1.19E−08 N.B. 3.67E−08 N.B. N.N. N.N.

ADI-24846 Infant 2301 N.B. N.B. N.B. 2.91E−08 N.N. N.N.

ADI-24847 Infant 2301 N.B. N.B. 4.00E−08 N.B. N.N. N.N.

ADI-24848 Infant 2301 2.08E−08 N.B. 3.56E−08 N.B. N.N. N.N.

ADI-24849 Infant 2301 1.71E−10 N.B. 1.17E−09 N.B. 0.01 0.03

ADI-24850 Infant 2301 3.84E−09 N.B. 5.56E−09 N.B. 0.94 4.17

ADI-24851 Infant 2301 N.B. 2.09E−08 N.B. N.B. N.N. N.N.

ADI-24852 Infant 2301 1.18E−08 9.57E−09 1.90E−08 9.17E−09 N.N. N.N.

ADI-24854 Infant 2301 N.B. N.B. 3.03E−08 N.B. N.N. N.N.

ADI-24855 Infant 2301 1.79E−08 N.B. 2.80E−08 N.B. N.N. N.N.

ADI-24856 Infant 2301 1.35E−08 N.B. 4.91E−09 N.B. N.N. N.N.

ADI-24857 Infant 2301 3.20E−09 N.B. 3.71E−09 N.B. 0.18 1.40

ADI-24858 Infant 2301 2.16E−08 N.B. 2.63E−08 N.B. N.N. N.N.

ADI-24859 Infant 2301 4.31E−09 N.B. 4.95E−09 N.B. 0.58 N.N.

ADI-24860 Infant 2301 1.08E−09 N.B. 1.56E−09 N.B. 0.06 0.09

ADI-24861 Infant 2301 3.01E−10 N.B. 4.61E−10 N.B. N.N. N.N.

ADI-24862 Infant 2301 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-24863 Infant 2301 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-19467 Infant 2021 9.13E−09 N.B. 3.77E−08 N.B. N.N. N.N.

ADI-19468 Infant 2021 2.22E−09 N.B. N.B. N.B. N.N. N.N.

ADI-19469 Infant 2021 1.74E−08 N.B. N.B. N.B. N.N. N.N.

ADI-19470 Infant 2021 2.97E−08 N.B. 1.97E−08 N.B. N.N. N.N.

ADI-19471 Infant 2021 3.23E−09 N.B. N.B. N.B. N.N. N.N.

ADI-19473 Infant 2021 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-19474 Infant 2021 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-19475 Infant 2021 1.43E−09 N.B. 4.25E−09 N.B. 0.05 0.04

ADI-19476 Infant 2021 N.B. 8.01E−10 N.B. 8.38E−10 N.N. N.N.

ADI-19478 Infant 2021 N.B. 3.86E−10 N.B. 7.13E−10 N.N. N.N.

ADI-19479 Infant 2021 N.B. 3.69E−09 N.B. 2.69E−09 N.N. N.N.

ADI-19480 Infant 2021 3.95E−10 1.29E−10 3.83E−10 1.19E−10 N.N. 6.25

ADI-19481 Infant 2021 7.60E−09 N.B. N.B. N.B. N.N. N.N.

ADI-19482 Infant 2021 1.28E−09 1.71E−09 1.89E−09 5.55E−10 1.49 2.24

ADI-19483 Infant 2021 1.72E−09 3.21E−10 1.77E−09 1.53E−10 N.N. N.N.

ADI-19484 Infant 2021 1.75E−09 3.69E−10 8.92E−09 3.55E−10 N.N. N.N.

ADI-19485 Infant 2021 3.56E−09 2.51E−10 N.B. P.F. N.N. N.N.

ADI-19486 Infant 2021 3.71E−09 5.25E−10 N.B. 7.55E−09 N.N. N.N.

ADI-19487 Infant 2021 N.B. N.B. N.B. N.B. N.N. 7.96

ADI-19488 Infant 2021 9.02E−09 N.B. 1.07E−08 N.B. N.N. 3.38

ADI-19489 Infant 2021 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-19490 Infant 2021 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-19491 Infant 2021 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-19492 Infant 2021 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-19493 Infant 2021 7.93E−09 N.B. 2.26E−08 N.B. N.N. N.N.

ADI-19494 Infant 2021 5.48E−09 N.B. N.B. N.B. 0.86 N.N.

ADI-19495 Infant 2021 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-19496 Infant 2021 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-19497 Infant 2021 N.B. P.F. N.B. 1.34E−08 N.N. N.N.

ADI-19498 Infant 2021 N.B. P.F. N.B. P.F. N.N. N.N.

ADI-19499 Infant 2021 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-19500 Infant 2021 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-19501 Infant 2021 4.46E−10 N.B. 1.59E−09 N.B. 0.02 0.02

ADI-19502 Infant 2021 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-19503 Infant 2021 N.B. N.B. N.B. 1.16E−08 N.N. N.N.

ADI-19505 Infant 2021 1.33E−08 4.94E−09 4.44E−08 5.01E−09 N.N. N.N.

ADI-22756 Infant 2201 7.85E−09 N.B. 5.58E−08 N.B. N.N. N.N.

ADI-22757 Infant 2201 3.10E−10 N.B. 5.38E−10 N.B. 0.06 0.07

ADI-22758 Infant 2201 6.32E−09 N.B. P.F. N.B. N.N. N.N.

ADI-22759 Infant 2201 2.97E−10 2.53E−08 3.53E−10 1.01E−08 0.08 0.20

ADI-22760 Infant 2201 5.21E−09 1.19E−09 3.07E−09 1.25E−09 N.N. N.N.

ADI-22762 Infant 2201 5.76E−08 P.F. N.B. N.B. N.N. N.N.

ADI-22763 Infant 2201 1.58E−09 3.19E−10 1.08E−08 5.33E−09 N.N. N.N.

ADI-22764 Infant 2201 2.27E−09 3.34E−10 1.42E−09 1.44E−09 N.N. N.N.

ADI-22765 Infant 2201 4.04E−08 N.B. P.F. N.B. N.N. N.N.

ADI-22766 Infant 2201 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-22767 Infant 2201 1.71E−08 N.B. P.F. N.B. N.N. N.N.

ADI-22768 Infant 2201 5.61E−09 3.41E−09 4.57E−09 N.B. N.N. N.N.

ADI-22769 Infant 2201 N.B. N.B. N.B. P.F. N.N. N.N.

ADI-22770 Infant 2201 N.B. P.F. N.B. P.F. N.N. N.N.

ADI-22771 Infant 2201 7.06E−09 N.B. 9.41E−09 N.B. N.N. N.N.

ADI-22772 Infant 2201 N.B. N.B. N.B. 5.02E−08 N.N. N.N.

ADI-22773 Infant 2201 P.F. N.B. N.B. N.B. N.N. N.N.

ADI-22774 Infant 2201 2.06E−09 N.B. 4.28E−09 N.B. 0.29 7.53

ADI-22775 Infant 2201 N.B. 3.00E−08 N.B. P.F. N.N. N.N.

ADI-22776 Infant 2201 N.B. N.B. P.F. N.B. N.N. N.N.

ADI-22777 Infant 2201 1.80E−09 2.68E−10 7.62E−10 2.24E−10 N.N. N.N.

ADI-22778 Infant 2201 6.22E−10 2.09E−10 4.02E−09 2.77E−09 N.N. N.N.

ADI-22779 Infant 2201 1.60E−08 6.20E−09 N.B. N.B. N.N. N.N.

ADI-22780 Infant 2201 N.B. 7.39E−10 2.38E−08 6.00E−10 N.N. N.N.

ADI-22781 Infant 2201 N.B. P.F. P.F. P.F. N.N. N.N.

ADI-14333 Infant 856 3.53E−10 N.B. 9.04E−10 N.B. 0.07 0.09

ADI-14334 Infant 856 3.16E−10 N.B. 6.22E−10 N.B. 0.05 0.11

ADI-14335 Infant 856 1.96E−10 N.B. 8.89E−10 N.B. 0.32 0.10

ADI-14336 Infant 856 3.12E−10 N.B. 2.65E−09 N.B. 0.07 0.09

ADI-14337 Infant 856 1.39E−09 N.B. 2.11E−09 N.B. 0.10 0.07

ADI-14338 Infant 856 8.41E−09 5.98E−09 7.04E−09 3.14E−09 N.N. 10.16

ADI-14339 Infant 856 2.45E−08 4.39E−10 1.77E−09 3.76E−10 N.N. N.N.

ADI-14340 Infant 856 4.11E−10 N.B. 9.80E−08 N.B. 6.63 1.94

ADI-14341 Infant 856 N.B. 7.13E−10 N.B. 6.12E−10 N.N. 17.46

ADI-14342 Infant 856 1.57E−09 4.95E−10 2.61E−08 P.F. 1.75 8.27

ADI-14343 Infant 856 1.85E−08 2.94E−09 3.81E−08 P.F. N.N. N.N.

ADI-14344 Infant 856 1.81E−10 N.B. 5.86E−10 N.B. 8.68 1.20

ADI-14345 Infant 856 6.32E−09 N.B. 5.26E−09 N.B. 2.30 0.87

ADI-14346 Infant 856 3.09E−10 N.B. 9.25E−10 N.B. 0.05 0.07

ADI-14347 Infant 856 4.99E−10 N.B. 2.54E−09 N.B. 0.11 0.05

ADI-14348 Infant 856 1.96E−09 5.66E−09 1.10E−07 N.B. N.N. N.N.

ADI-14349 Infant 856 5.33E−09 N.B. 4.07E−09 N.B. N.N. 1.84

ADI-14350 Infant 856 3.73E−09 2.64E−10 5.74E−10 1.48E−10 N.N. 4.82

ADI-14351 Infant 856 2.21E−08 3.61E−10 7.89E−10 2.15E−10 N.N. N.N.

ADI-14352 Infant 856 N.B. 4.48E−10 5.54E−09 3.83E−10 N.N. N.N.

ADI-14353 Infant 856 1.40E−08 2.60E−10 1.26E−08 P.F. N.N. 14.62

ADI-14354 Infant 856 9.98E−09 1.04E−09 2.53E−08 6.63E−09 N.N. N.N.

ADI-14355 Infant 856 6.60E−09 4.80E−10 1.25E−09 3.70E−10 N.N. 4.72

ADI-14356 Infant 856 N.B. 3.90E−09 1.30E−08 4.98E−09 N.N. N.N.

ADI-14357 Infant 856 1.76E−10 N.B. 3.06E−10 N.B. 1.24 0.88

ADI-14358 Infant 856 5.91E−09 6.56E−10 6.03E−08 2.75E−08 N.N. N.N.

ADI-14359 Infant 856 N.B. 4.11E−09 3.46E−08 P.F. N.N. N.N.

ADI-14360 Infant 856 N.B. 5.88E−09 2.68E−08 9.03E−09 N.N. N.N.

ADI-14361 Infant 856 N.B. 4.37E−10 5.28E−08 2.93E−10 N.N. N.N.

ADI-14362 Infant 856 3.15E−09 1.57E−08 1.19E−07 N.B. N.N. N.N.

ADI-14363 Infant 856 3.54E−09 N.B. 5.35E−09 N.B. N.N. N.N.

ADI-14364 Infant 856 6.30E−10 N.B. 6.16E−08 N.B. 0.03 2.39

ADI-14365 Infant 856 1.19E−09 1.03E−08 9.62E−10 2.23E−08 0.80 0.49

ADI-14366 Infant 856 6.14E−09 N.B. 1.80E−08 N.B. N.N. N.N.

ADI-14367 Infant 856 1.57E−10 N.B. 2.69E−10 N.B. 3.94 0.33

ADI-14368 Infant 856 2.60E−09 2.45E−08 1.21E−09 1.77E−08 N.N. 1.10

ADI-14369 Infant 856 N.B. 1.22E−09 3.38E−09 9.00E−10 N.N. N.N.

ADI-14370 Infant 856 8.12E−09 N.B. 4.18E−09 N.B. N.N. 1.38

ADI-14371 Infant 856 N.B. 1.23E−09 8.43E−09 1.07E−09 N.N. N.N.

ADI-14372 Infant 856 N.B. 6.59E−10 N.B. 4.43E−09 N.N. N.N.

ADI-14373 Infant 856 1.96E−09 1.06E−09 1.59E−08 N.B. N.N. N.N.

ADI-14374 Infant 856 4.61E−09 N.B. 2.09E−09 N.B. N.N. 0.86

ADI-14375 Infant 856 N.B. 4.77E−10 3.21E−09 3.31E−09 N.N. N.N.

ADI-14376 Infant 856 P.F. P.F. P.F. P.F. N.N. N.N.

ADI-14377 Infant 856 6.64E−09 N.B. 5.28E−09 N.B. N.N. 2.13

ADI-14378 Infant 856 5.87E−09 N.B. 6.10E−09 N.B. N.N. 21.58

ADI-14379 Infant 856 N.B. 3.29E−09 N.B. 2.35E−09 N.N. N.N.

ADI-14380 Infant 856 6.04E−09 N.B. 1.08E−08 N.B. N.N. N.N.

ADI-14381 Infant 856 2.20E−09 7.54E−10 3.67E−08 P.F. ND ND

ADI-14382 Infant 856 N.B. 8.46E−10 N.B. N.B. N.N. N.N.

ADI-14383 Infant 856 N.B. 4.34E−10 1.75E−09 2.51E−10 N.N. N.N.

ADI-14384 Infant 856 3.71E−09 4.69E−10 4.78E−09 N.B. N.N. N.N.

ADI-14385 Infant 856 8.72E−08 P.F. P.F. P.F. N.N. N.N.

ADI-14386 Infant 856 6.29E−09 1.32E−09 3.04E−09 P.F. N.N. N.N.

ADI-14388 Infant 856 5.58E−09 N.B. 5.50E−09 N.B. N.N. 3.07

ADI-14389 Infant 856 N.B. 2.29E−08 8.15E−08 P.F. N.N. N.N.

ADI-14390 Infant 856 N.B. N.B. N.B. N.B. N.N. N.N.

ADI-14391 Infant 856 6.95E−09 N.B. 5.36E−09 N.B. N.N. 22.25

ADI-14392 Infant 856 7.56E−09 N.B. 7.25E−08 N.B. N.N. N.N.

ADI-14393 Infant 856 3.11E−10 N.B. 4.74E−10 1.17E−08 ND ND

ADI-14394 Infant 856 1.15E−08 N.B. P.F. N.B. N.N. N.N.

ADI-14395 Infant 856 2.49E−08 N.B. P.F. N.B. N.N. N.N.

ADI-14396 Infant 856 N.B. N.B. 1.55E−08 N.B. N.N. N.N.

ADI-14397 Infant 856 2.85E−08 N.B. P.F. N.B. N.N. N.N.

ADI-14399 Infant 856 1.89E−10 N.B. 3.65E−10 N.B. 0.97 0.46

ADI-14400 Infant 856 2.90E−10 N.B. 4.51E−10 N.B. ND 3.71

ADI-14401 Infant 856 1.19E−09 N.B. 2.17E−09 N.B. 0.05 0.06

ADI-14402 Infant 856 2.79E−10 N.B. 4.16E−10 N.B. 0.02 0.03

ADI-14403 Infant 856 5.09E−10 N.B. 6.99E−10 N.B. 0.08 0.N.N.1

ADI-14404 Infant 856 N.B. 6.27E−10 N.B. 4.98E−10 N.N. N.N.

ADI-14405 Infant 856 1.42E−10 1.17E−08 2.27E−10 3.80E−08 0.04 0.04

ADI-14406 Infant 856 6.85E−09 3.39E−10 9.06E−10 4.73E−10 N.N. N.N.

ADI-14407 Infant 856 6.28E−09 3.78E−10 1.14E−08 P.F. N.N. N.N.

ADI-14408 Infant 856 8.53E−09 2.14E−09 1.28E−08 P.F. N.N. N.N.

ADI-14409 Infant 856 1.50E−10 N.B. 2.89E−10 N.B. 0.29 0.23

ADI-14410 Infant 856 3.77E−09 N.B. 1.71E−08 N.B. 1.22 2.64

ADI-14411 Infant 856 6.12E−09 N.B. 3.92E−09 N.B. 9.27 1.96

ADI-14412 Infant 856 5.60E−09 N.B. 1.34E−08 N.B. N.N. N.N.

ADI-14413 Infant 856 5.45E−09 N.B. 2.71E−09 N.B. 15.13 1.69

ADI-14414 Infant 856 5.00E−09 N.B. 3.07E−09 N.B. N.N. N.N.

ADI-14415 Infant 856 4.20E−09 N.B. 3.51E−09 N.B. N.N. N.N.

ADI-14416 Infant 856 2.39E−09 1.82E−10 3.69E−10 1.06E−10 N.N. N.N.

ADI-14417 Infant 856 N.B. 1.63E−09 N.B. 3.99E−09 ND ND

ADI-14418 Infant 856 1.25E−09 4.41E−10 1.58E−09 2.58E−10 0.30 0.66

ADI-14419 Infant 856 2.69E−09 N.B. N.B. N.B. N.N. N.N.

ADI-14420 Infant 856 6.35E−09 N.B. 4.32E−09 N.B. N.N. N.N.

ADI-14421 Infant 856 N.B. 1.07E−09 2.82E−09 7.40E−10 N.N. N.N.

ADI-14422 Infant 856 1.14E−08 4.76E−09 3.39E−08 N.B. N.N. N.N.

ADI-14423 Infant 856 9.65E−09 N.B. 3.40E−09 N.B. N.N. N.N.

ADI-14424 Infant 856 3.43E−09 N.B. 1.90E−09 N.B. N.N. 2.48

ADI-14425 Infant 856 4.81E−08 7.42E−10 2.03E−08 9.34E−09 N.N. N.N.

ADI-14426 Infant 856 2.38E−08 3.96E−10 1.92E−08 P.F. N.N. N.N.

ADI-14427 Infant 856 2.34E−10 3.33E−09 1.08E−08 N.B. 0.25 N.N.

ADI-14428 Infant 856 4.22E−08 N.B. 1.41E−08 N.B. N.N. N.N.

ADI-14654 Infant 856 2.04E−09 N.B. 7.64E−09 N.B. N.N. N.N.

ADI-14655 Infant 856 1.69E−08 P.F. 1.40E−08 P.F. N.N. N.N.

ADI-14656 Infant 856 P.F. 3.70E−10 2.51E−08 P.F. N.N. N.N.

ADI-14657 Infant 856 2.84E−09 N.B. N.B. N.B. N.N. N.N.

ADI-14658 Infant 856 N.B. 1.58E−08 N.B. 1.79E−08 N.N. N.N.

ADI-14659 Infant 856 4.86E−09 N.B. 3.71E−09 N.B. N.N. 5.56

ADI-14571 Infant 856 2.91E−09 N.B. N.B. N.B. N.N. 3.06

ADI-14572 Infant 856 N.B. 1.70E−08 P.F. N.B. N.N. N.N.

ADI-14573 Infant 856 N.B. 3.73E−10 2.10E−08 3.55E−09 N.N. N.N.

ADI-14575 Infant 856 1.12E−08 P.F. N.B. N.B. N.N. N.N.

ADI-14576 Infant 856 6.97E−09 N.B. 1.93E−08 N.B. 3.11 0.77

ADI-14577 Infant 856 4.39E−10 N.B. 2.19E−09 N.B. 0.04 0.05

ADI-14578 Infant 856 3.29E−09 N.B. 4.02E−09 N.B. N.N. N.N.

ADI-14579 Infant 856 7.54E−09 P.F. 3.73E−09 N.B. N.N. N.N.

ADI-14580 Infant 856 6.70E−09 N.B. 4.54E−09 N.B. N.N. 3.75

ADI-14581 Infant 856 N.B. N.B. 2.88E−09 N.B. N.N. 6.25

ADI-14582 Infant 856 5.82E−09 N.B. 1.81E−09 N.B. ND ND

ADI-14583 Infant 856 4.74E−10 N.B. 1.59E−09 N.B. 0.05 0.06

ADI-14584 Infant 856 P.F. N.B. 4.76E−10 N.B. 1.53 0.65

ADI-14585 Infant 856 2.72E−10 N.B. 4.49E−10 N.B. 0.02 0.03

ADI-14586 Infant 856 4.52E−10 N.B. 6.70E−09 N.B. 0.05 0.50

ADI-14587 Infant 856 6.09E−10 N.B. 8.33E−10 N.B. 0.15 0.11

ADI-14588 Infant 856 3.24E−09 N.B. 1.48E−09 N.B. 13.60 0.59

ADI-14589 Infant 856 6.48E−09 5.96E−10 2.82E−08 1.54E−08 N.N. N.N.

ADI-14590 Infant 856 1.32E−08 2.68E−09 5.99E−09 9.67E−10 N.N. N.N.

ADI-14591 Infant 856 1.87E−10 N.B. 5.54E−10 N.B. N.N. 9.36

ADI-14592 Infant 856 2.40E−09 1.36E−10 3.01E−10 9.32E−11 N.N. N.N.

ADI-14593 Infant 856 2.33E−09 1.61E−10 3.58E−10 1.08E−10 2.28 4.03

ADI-14594 Infant 856 N.B. 2.57E−10 1.82E−08 2.14E−10 N.N. N.N.

ADI-14595 Infant 856 2.19E−09 1.30E−09 1.60E−08 1.44E−08 ND ND

ADI-14596 Infant 856 1.86E−10 N.B. 1.86E−09 N.B. N.N. N.N.

ADI-14597 Infant 856 5.26E−09 N.B. 1.67E−09 N.B. N.N. 3.05

ADI-14598 Infant 856 P.F. 4.52E−10 7.07E−09 4.81E−09 N.N. N.N.

ADI-14599 Infant 856 1.02E−10 6.36E−10 6.22E−10 3.58E−10 0.14 1.11

ADI-14600 Infant 856 7.58E−10 N.B. 9.86E−10 N.B. 0.12 0.08

ADI-14601 Infant 856 3.79E−09 N.B. 1.96E−09 N.B. 12.19 3.10

ADI-14602 Infant 856 4.73E−09 N.B. 8.94E−09 N.B. N.N. 6.53

ADI-14603 Infant 856 8.40E−09 N.B. 3.05E−08 N.B. N.N. 2.03

ADI-14604 Infant 856 2.44E−09 N.B. 1.53E−09 N.B. N.N. N.N.

ADI-14605 Infant 856 N.B. 9.24E−10 2.72E−09 3.99E−10 N.N. N.N.

ADI-14606 Infant 856 N.B. 1.28E−09 N.B. 6.59E−10 0.85 0.29

ADI-14607 Infant 856 1.70E−09 3.81E−10 6.40E−10 2.27E−10 N.N. 0.13

ADI-20959 Infant 2042 3.37E−10 N.B. 4.30E−10 N.B. 0.06 0.28

ADI-20960 Infant 2042 2.20E−10 1.63E−10 2.30E−10 1.63E−10 0.35 0.71

ADI-20961 Infant 2042 3.74E−10 N.B. 5.04E−10 N.B. 0.09 0.32

ADI-20962 Infant 2042 2.89E−10 N.B. 4.63E−10 N.B. 0.07 0.15

ADI-20963 Infant 2042 7.91E−10 9.09E−11 3.14E−09 6.14E−10 N.N. N.N.

ADI-20964 Infant 2042 3.60E−10 N.B. 2.49E−09 N.B. 0.06 0.14

ADI-20965 Infant 2042 1.21E−10 P.F. 5.33E−10 P.F. 0.32 0.64

ADI-20966 Infant 2042 3.06E−10 N.B. 8.62E−10 N.B. 0.00 0.13

ADI-20967 Infant 2042 2.23E−09 2.57E−10 4.08E−09 3.45E−09 N.N. N.N.

ADI-20968 Infant 2042 1.35E−10 1.57E−10 1.27E−10 1.50E−10 0.14 0.44

ADI-20969 Infant 2042 3.01E−10 N.B. 4.09E−10 N.B. 0.12 0.27

ADI-20970 Infant 2042 1.83E−09 N.B. 2.55E−09 N.B. 2.14 2.92

ADI-20971 Infant 2042 3.33E−10 N.B. 5.44E−10 N.B. N.N. N.N.

ADI-20972 Infant 2042 8.88E−10 4.01E−10 6.06E−09 3.48E−09 N.N. N.N.

ADI-20973 Infant 2042 3.08E−10 N.B. 4.17E−10 N.B. 0.03 0.19

ADI-20974 Infant 2042 2.91E−10 N.B. 3.60E−10 N.B. 0.00 0.09

ADI-20975 Infant 2042 9.20E−11 1.46E−10 9.58E−11 1.29E−10 0.05 0.49

ADI-20976 Infant 2042 1.86E−09 2.63E−10 9.55E−10 3.04E−10 N.N. N.N.

ADI-20977 Infant 2042 1.51E−10 N.B. P.F. N.B. N.N. N.N.

ADI-20978 Infant 2042 2.90E−10 N.B. 3.19E−10 N.B. 0.01 0.17

ADI-20979 Infant 2042 9.79E−10 N.B. 4.00E−09 N.B. 0.29 0.21

ADI-20980 Infant 2042 2.00E−10 N.B. 5.42E−10 N.B. N.N. N.N.

ADI-20981 Infant 2042 2.34E−09 2.33E−10 2.14E−09 2.95E−10 N.N. N.N.

ADI-20982 Infant 2042 4.88E−09 N.B. 5.45E−09 N.B. N.N. N.N.

ADI-20983 Infant 2042 2.13E−10 2.05E−09 1.17E−09 P.F. N.N. N.N.

ADI-20984 Infant 2042 3.29E−09 N.B. 2.02E−08 N.B. N.N. N.N.

ADI-20986 Infant 2042 4.14E−10 N.B. 1.25E−09 N.B. 0.02 0.19

ADI-20987 Infant 2042 4.63E−09 N.B. 3.56E−08 N.B. N.N. N.N.

ADI-20988 Infant 2042 2.94E−10 N.B. 1.29E−09 N.B. 0.06 0.27

ADI-20989 Infant 2042 4.80E−09 4.28E−10 6.29E−09 8.09E−10 N.N. N.N.

ADI-20990 Infant 2042 1.58E−09 1.78E−10 9.04E−10 3.12E−10 N.N. N.N.

ADI-20991 Infant 2042 2.34E−10 N.B. 2.58E−10 N.B. 0.14 0.19

ADI-20992 Infant 2042 9.56E−10 N.B. 1.22E−09 N.B. 0.04 0.64

ADI-20993 Infant 2042 1.38E−09 1.68E−10 7.42E−10 2.73E−10 N.N. N.N.

ADI-20994 Infant 2042 8.94E−11 P.F. 1.09E−10 P.F. 0.06 0.18

ADI-20995 Infant 2042 2.60E−09 N.B 1.36E−08 N.B ND ND

ADI-20996 Infant 2042 1.03E−09 2.04E−10 1.06E−09 1.12E−09 N.N. N.N.

ADI-20997 Infant 2042 1.78E−09 1.97E−10 3.09E−09 6.09E−10 N.N. N.N.

ADI-20998 Infant 2042 2.57E−10 N.B. 1.35E−09 N.B. 0.03 N.N.

ADI-20999 Infant 2042 4.16E−09 N.B. 2.41E−08 N.B. N.N. N.N.

ADI-21000 Infant 2042 1.49E−09 2.95E−10 1.30E−09 6.02E−10 N.N. N.N.

ADI-21001 Infant 2042 2.12E−09 2.77E−10 1.85E−09 3.02E−10 N.N. N.N.

ADI-21002 Infant 2042 2.36E−09 2.14E−10 8.60E−09 6.39E−09 N.N. N.N.

ADI-21003 Infant 2042 4.75E−09 4.40E−10 9.87E−10 4.21E−10 N.N. N.N.

ADI-21004 Infant 2042 4.59E−09 5.40E−10 1.02E−08 7.98E−10 N.N. 4.78

ADI-21005 Infant 2042 3.37E−09 N.B. 7.70E−09 N.B. N.N. N.N.

ADI-21006 Infant 2042 1.04E−08 N.B. N.B. N.B. N.N. N.N.

ADI-21007 Infant 2042 1.48E−09 1.71E−10 1.72E−09 1.71E−10 N.N. N.N.

ADI-21008 Infant 2042 5.68E−09 9.18E−10 4.14E−09 1.45E−09 N.N. N.N.

ADI-21009 Infant 2042 4.88E−09 N.B. 1.95E−08 N.B. N.N. N.N.

ADI-21010 Infant 2042 3.58E−09 N.B. N.B. N.B. N.N. N.N.

ADI-21011 Infant 2042 1.41E−09 1.62E−10 9.82E−10 3.56E−10 N.N. N.N.

ADI-21012 Infant 2042 3.71E−10 2.14E−10 1.92E−09 2.80E−10 N.N. N.N.

ADI-21013 Infant 2042 2.29E−09 N.B. 1.79E−09 N.B. 0.08 0.14

ADI-21014 Infant 2042 4.08E−10 N.B. 3.78E−10 N.B. 0.05 0.17

ADI-21015 Infant 2042 4.41E−09 N.B. 3.24E−08 N.B. 1.46 1.15

ADI-21017 Infant 2042 3.05E−10 N.B. 1.56E−09 N.B. N.N. N.N.

ADI-21018 Infant 2042 3.50E−10 N.B. 3.66E−10 N.B. 0.24 0.34

ADI-21019 Infant 2042 1.82E−10 1.54E−10 9.62E−10 1.68E−10 6.25 6.25

ADI-21021 Infant 2042 2.55E−09 N.B. 4.50E−09 N.B. N.N. N.N.

ADI-21022 Infant 2042 N.B. 2.56E−10 1.74E−08 3.57E−10 N.N. N.N.

ADI-21023 Infant 2042 2.64E−10 N.B. 3.16E−10 N.B. 0.12 0.26

ADI-21025 Infant 2042 2.42E−10 N.B. 2.95E−10 N.B. 0.09 0.19

ADI-21026 Infant 2042 6.35E−09 9.45E−10 3.99E−09 1.43E−09 N.N. N.N.

ADI-21027 Infant 2042 2.96E−10 N.B. 3.40E−10 N.B. 0.13 0.27

ADI-21028 Infant 2042 5.45E−09 N.B. 3.33E−09 N.B. N.N. 9.09

ADI-21029 Infant 2042 3.77E−09 N.B. 8.38E−09 N.B. N.N. 0.96

ADI-21030 Infant 2042 2.57E−10 N.B. 3.01E−10 N.B. 0.16 0.26

ADI-21031 Infant 2042 1.07E−09 N.B. 1.50E−09 N.B. 0.31 3.36

ADI-21032 Infant 2042 2.96E−10 N.B. 3.44E−10 N.B. 0.10 0.30

ADI-21033 Infant 2042 1.93E−10 N.B. 1.40E−09 N.B. 4.64 9.20

ADI-21034 Infant 2042 1.45E−10 N.B. 1.74E−10 N.B. N.N. 7.30

ADI-21035 Infant 2042 1.03E−08 N.B. N.B. N.B. N.N. N.N.

ADI-21036 Infant 2042 5.52E−09 N.B. N.B. N.B. N.N. N.N.

ADI-21037 Infant 2042 1.95E−09 2.48E−10 4.81E−09 3.17E−09 N.N. N.N.

ADI-21038 Infant 2042 2.93E−09 1.45E−09 1.60E−08 N.B. N.N. N.N.

ADI-21039 Infant 2042 1.71E−09 2.40E−10 1.27E−08 6.31E−09 N.N. N.N.

ADI-21040 Infant 2042 N.B. 7.77E−10 N.B. 1.03E−09 N.N. N.N.

ADI-21041 Infant 2042 7.30E−09 N.B. N.B. N.B. N.N. N.N.

ADI-21042 Infant 2042 2.96E−09 2.87E−10 1.18E−09 3.98E−10 N.N. N.N.

ADI-21043 Infant 2042 1.11E−10 1.65E−09 1.54E−10 1.93E−09 0.19 0.08

ADI-21044 Infant 2042 4.51E−09 N.B. 5.85E−09 N.B. N.N. 2.13

ADI-21045 Infant 2042 4.56E−10 N.B. 5.96E−10 N.B. 0.04 0.09

ADI-21046 Infant 2042 1.66E−09 1.87E−10 6.94E−10 2.24E−10 N.N. N.N.

ADI-21047 Infant 2042 2.11E−09 2.90E−10 7.56E−10 2.62E−10 N.N. N.N.

ADI-21048 Infant 2042 1.11E−10 P.F. P.F. P.F. 0.08 0.16

ADI-21049 Infant 2042 3.97E−10 N.B. 1.27E−09 N.B. 0.62 0.56

ADI-21050 Infant 2042 3.62E−10 N.B. 3.23E−10 N.B. 0.08 0.12

ADI-21051 Infant 2042 2.92E−10 N.B. 3.35E−10 N.B. N.N. N.N.

ADI-21052 Infant 2042 1.26E−10 1.84E−08 1.10E−10 P.F. 0.05 0.11

ADI-21053 Infant 2042 7.10E−08 6.37E−09 N.B. 1.18E−07 N.N. N.N.

ADI-21054 Infant 2042 1.85E−10 3.72E−10 1.39E−10 3.06E−10 0.09 0.49

ADI-21055 Infant 2042 1.10E−09 1.85E−10 2.98E−09 4.35E−09 ND ND

ADI-21056 Infant 2042 2.51E−10 7.22E−08 2.23E−10 6.34E−08 0.00 0.02

ADI-21057 Infant 2042 9.36E−10 N.B. 8.60E−10 N.B. 0.00 0.00

ADI-21058 Infant 2042 9.72E−10 N.B. 5.15E−10 N.B. 0.04 0.48

ADI-21059 Infant 2042 3.05E−09 N.B. 9.43E−09 N.B. N.N. 0.30

ADI-21060 Infant 2042 4.26E−10 N.B. 3.49E−10 N.B. 0.06 0.14

ADI-21061 Infant 2042 1.10E−09 1.42E−10 2.76E−09 2.48E−09 N.N. N.N.

ADI-21062 Infant 2042 1.24E−09 2.36E−10 8.27E−10 4.17E−10 N.N. N.N.

ADI-21063 Infant 2042 8.34E−10 N.B. 7.77E−10 N.B. 0.04 0.11

ADI-21064 Infant 2042 3.20E−10 N.B. 2.80E−10 N.B. 0.03 0.12

ADI-21065 Infant 2042 1.71E−10 N.B. P.F. N.B. N.N. N.N.

ADI-21067 Infant 2042 3.98E−09 N.B 5.90E−09 N.B ND ND

ADI-21068 Infant 2042 2.55E−10 1.55E−08 2.38E−10 7.85E−09 0.10 N.N.

ADI-21069 Infant 2042 1.23E−10 P.F. 1.19E−10 P.F. 0.11 0.26

ADI-21070 Infant 2042 5.37E−09 N.B. 7.59E−09 N.B. N.N. 2.38

ADI-21071 Infant 2042 1.17E−09 2.16E−10 1.88E−09 1.38E−09 N.N. N.N.

ADI-21072 Infant 2042 3.41E−10 N.B. 3.32E−10 N.B. 0.04 0.33

ADI-21073 Infant 2042 4.06E−09 5.80E−10 1.78E−09 6.75E−10 ND 11.15

ADI-21075 Infant 2042 4.07E−10 N.B. 5.15E−10 N.B. 0.03 0.48

ADI-21076 Infant 2042 2.19E−10 7.34E−09 1.96E−10 6.28E−09 0.03 0.30

ADI-21077 Infant 2042 4.28E−10 N.B. 3.83E−10 N.B. 0.06 0.06

ADI-21078 Infant 2042 3.11E−10 N.B. 3.07E−10 N.B. 0.03 0.20

ADI-21079 Infant 2042 3.13E−10 N.B. 3.08E−10 N.B. 0.20 0.29

ADI-21080 Infant 2042 3.60E−10 N.B. 3.72E−10 N.B. 0.10 0.17

ADI-21081 Infant 2042 2.84E−10 N.B. 2.77E−10 N.B. 0.10 0.32

ADI-21082 Infant 2042 2.85E−10 N.B. 2.81E−10 6.17E−09 0.09 0.25

ADI-21083 Infant 2042 2.25E−09 N.B. 2.65E−09 N.B. 0.36 0.79

ADI-21084 Infant 2042 1.09E−10 1.73E−08 1.04E−10 2.29E−08 0.14 0.46

ADI-21085 Infant 2042 3.07E−10 N.B. 3.09E−10 6.24E−09 0.10 0.48

ADI-21086 Infant 2042 2.90E−10 N.B. 2.76E−10 N.B. 0.11 0.47

ADI-21087 Infant 2042 N.B. 5.45E−10 N.B. 4.76E−10 N.N. N.N.

ADI-21089 Infant 2042 2.82E−10 N.B. 2.62E−10 3.34E−09 0.27 0.17

ADI-21090 Infant 2042 1.17E−09 1.76E−10 4.89E−10 1.75E−10 ND ND

ADI-21091 Infant 2042 7.49E−10 N.B. 1.39E−09 N.B. 0.29 0.92

Number of Number of

Antigenic VH LC nucleotide nucleotide

Site PSR germline germline substitutions substitutions

Name Assignment Score gene usage gene usage in VH in VL

ADI-25462 Site III 0.001 VH3-21 VL1-40 1 0

ADI-25467 Unknown 0.000 VH4-59 VK1-39 0 0

ADI-25468 Unknown 0.402 VH5-51 VL3-1 0 0

ADI-25472 Site III 0.000 VH3-21 VL1-40 0 0

ADI-25478 Site III 0.817 VH3-21 VL1-40 0 0

ADI-25479 Site III 0.373 VH3-21 VL1-40 0 0

ADI-25480 Site III 0.340 VH3-21 VL1-40 0 0

ADI-25484 Site III 0.000 VH3-21 VL1-40 0 0

ADI-25491 Site I 0.000 VH4-31 VL3-1 0 0

ADI-25495 Site III 0.000 VH3-21 VL2-14 0 1

ADI-25496 Unknown 0.000 VH3-21 VL1-40 0 0

ADI-25497 Site III 0.000 VH3-7 VK1D-16 0 0

ADI-25502 Site III 0.043 VH1-69 VL3-27 0 1

ADI-25503 Site III 0.277 VH1-69 VL3-1 0 0

ADI-25505 Site III 0.000 VH3-21 VL1-40 0 0

ADI-25514 Site II 0.493 VH1-69 VL3-1 0 0

ADI-25517 Site I 0.107 VH1-2 VL2-14 0 1

ADI-25518 Site I 0.116 VH1-2 VL2-14 0 1

ADI-25524 Site III 0.000 VH3-21 VL1-40 0 0

ADI-25532 Site III 0.000 VH3-21 VL1-40 0 0

ADI-25533 Site I 0.006 VH1-2 VL2-14 0 1

ADI-25542 Site I 0.000 VH3-23 VL8-61 0 0

ADI-25547 Unknown 0.000 VH3-53 VK1-12 0 0

ADI-25548 Unknown 0.010 VH3-53 VL2-11 0 0

ADI-25549 Site III 0.702 VH3-21 VL1-40 0 0

ADI-25555 Site III 0.029 VH3-21 VL1-40 0 0

ADI-25556 Site III 0.000 VH3-21 VL1-40 0 0

ADI-25557 Site III 0.000 VH3-21 VL1-40 0 0

ADI-25559 Site III 0.000 VH3-21 VL1-40 0 0

ADI-25562 Site III 0.105 VH3-11 VL1-40 0 0

ADI-25565 Site III 0.108 VH3-21 VL1-40 0 0

ADI-25567 Site I 0.000 VH4-34 VK4-1 0 0

ADI-25569 Site I 0.000 VH3-74 VL3-25 0 1

ADI-25572 Site IV 0.184 VH1-2 VK2-28 0 0

ADI-25573 Unknown 0.000 VH1-46 VL3-21 0 1

ADI-25575 Unknown 0.000 VH1-46 VL3-21 0 0

ADI-25576 Site I 0.000 VH3-74 VL6-57 0 0

ADI-25577 Site III 0.028 VH3-21 VL1-40 0 0

ADI-25587 Unknown 0.000 VH3-33 VL2-14 0 1

ADI-25588 Site III 0.100 VH3-21 VL1-40 0 0

ADI-25595 Site III 0.012 VH3-21 VL1-40 0 0

ADI-25598 Site I 0.106 VH4-39 VL3-25 5 1

ADI-19420 Site III 0.709 VH3-21 VL1-40 0 0

ADI-19421 Site III 0.120 VH3-30 VL2-14 0 1

ADI-19422 Site IV 0.102 VH3-30 VL3-21 0 0

ADI-19424 Site IV 0.020 VH3-66 VL3-21 4 0

ADI-19425 Site III 0.007 VH3-21 VL1-40 0 0

ADI-19426 Site IV 0.023 VH4-59 VL3-1 0 0

ADI-19427 Site III 0.022 VH3-21 VL1-40 3 4

ADI-19428 Site III 0.058 VH3-21 VL1-40 0 0

ADI-19429 Site I 0.616 VH4-39 VL1-40 0 0

ADI-19430 Site I 0.744 VH1-69 VK2-28 0 0

ADI-19431 Site III 0.068 VH3-21 VL1-40 0 0

ADI-19432 Site IV 0.000 VH1-46 VK1-05 0 0

ADI-19433 Site III 0.000 VH3-21 VL1-40 0 0

ADI-19435 Site I 0.000 VH4-61 VL3-01 0 1

ADI-19436 Site I 0.073 VH4-39 VL3-1 0 0

ADI-19437 Unknown 0.000 VH1-18 VK1-12 0 0

ADI-19439 Site III 0.000 VH3-23 VK1-05 0 0

ADI-19440 Site III 0.000 VH3-48 VL1-40 0 0

ADI-19441 Site I 0.417 VH1-69 VK1-39 0 0

ADI-19444 Site V 0.000 VH1-18 VK4-01 0 0

ADI-19445 Unknown 0.002 VH4-4 VL3-21 0 1

ADI-19447 Site III 0.029 VH4-39 VL3-01 0 0

ADI-19448 Site III 0.000 VH3-21 VL1-40 0 0

ADI-19449 Site III 0.142 VH3-21 VL1-40 0 0

ADI-19450 Unknown 0.000 VH3-23 VK1-05 0 0

ADI-19454 Site III 0.012 VH3-21 VL2-14 0 1

ADI-19455 Site III 0.007 VH3-21 VL1-40 0 0

ADI-19457 Site III 0.000 VH3-21 VL1-40 0 0

ADI-19458 Site III 0.101 VH3-21 VL1-40 3 0

ADI-19459 Site IV 0.026 VH3-66 VL3-21 0 0

ADI-19460 Site I 0.076 VH4-34 VK1-39 0 0

ADI-19461 Site II 0.000 VH3-11 VL3-21 0 0

ADI-19462 Site IV 0.000 VH2-5 VK1-5 0 0

ADI-19463 Unknown 0.065 VH4-304 VK4-1 0 0

ADI-19465 Site III 0.000 VH3-21 VL1-40 0 0

ADI-19506 Unknown 0.424 VH1-18 VK2-28 0 0

ADI-19507 Site III 0.000 VH3-21 VL1-40 0 0

ADI-19509 Site III 0.000 VH3-21 VL1-40 0 0

ADI-19510 Site III 0.108 VH3-21 N/A 6 2

ADI-19511 Unknown 0.444 VH2-5 VK1-17 0 0

ADI-24792 Site III 0.000 VH3-11 VL1-40 5 2

ADI-24793 Site I 0.000 VH5-51 VL6-57 1 2

ADI-24795 Site III 0.000 VH3-21 VL1-40 0 0

ADI-24796 Unknown 0.000 VH3-33 VL3-1 0 0

ADI-24798 Site I 0.000 VH4-59 VL3-1 0 0

ADI-24799 Site III 0.000 VH3-21 VL1-40 0 0

ADI-24800 Site III 0.843 VH3-21 VL1-40 0 2

ADI-24801 Site III 0.158 VH1-18 VL3-1 0 1

ADI-24803 Unknown 0.077 VH3-23 VK3-20 6 3

ADI-24805 Site III 0.000 VH3-21 VL1-40 0 0

ADI-24807 Site I 0.083 VH4-39 VL3-1 0 0

ADI-24808 Site I 0.000 VH1-2 VL2-8 0 0

ADI-24811 Site IV 0.112 VH1-8 VL3-21 0 0

ADI-24812 Site V 0.000 VH3-23 VL3-25 4 1

ADI-24813 Site IV 0.000 VH3-9 VL1-40 0 0

ADI-24814 Site IV 0.117 VH3-30 VK3-20 2 3

ADI-24815 Site III 0.000 VH3-21 VL1-40 0 0

ADI-24816 Site I 0.102 VH1-8 VL3-1 0 0

ADI-24817 Site III 0.000 VH3-21 VL1-40 0 0

ADI-24818 Site I 0.000 VH1-2 VL2-14 0 1

ADI-24819 Site III 0.000 VH3-21 VL1-40 0 0

ADI-24820 Unknown 0.248 VH1-69 VK1-39 0 0

ADI-24821 Site II 0.000 VH3-9 VL1-44 0 0

ADI-24822 Site III 0.000 VH3-21 VL1-40 0 0

ADI-24823 Site III 0.000 VH3-21 VL1-40 0 0

ADI-24824 Site III 0.000 VH4-59 VK1-8 0 0

ADI-24825 Unknown 0.338 VH1-8 VK2-28 0 0

ADI-24826 Site III 0.102 VH3-21 VL2-14 0 1

ADI-24827 Site 0 0.000 VH3-66 VK3-15 1 0

ADI-24828 Site III 0.109 VH3-21 VL1-40 9 2

ADI-24829 Site III 0.000 VH3-21 VL1-40 0 0

ADI-24830 Site V 0.000 VH1-69 VK2-28 0 0

ADI-24831 Site III 0.164 VH3-21 VL1-40 0 0

ADI-24832 Site III 0.360 VH3-21 VL1-40 6 1

ADI-24833 Site III 0.000 VH3-21 VL1-40 0 0

ADI-24834 Site I 0.293 VH3-23 VK1-5 1 1

ADI-24835 Site III 0.000 VH3-21 VL1-40 5 5

ADI-24836 Unknown 0.106 VH3-9 VK1-39 0 0

ADI-24837 Unknown 0.000 VH4-59 VL1-51 0 0

ADI-24838 Site III 0.122 VH3-21 VL1-40 0 0

ADI-24839 Site III 0.000 VH3-21 VL1-40 0 0

ADI-24840 Site III 0.000 VH3-21 VL1-40 0 0

ADI-24841 Unknown 0.144 VH1-3 VK3-15 0 0

ADI-24842 Site III 0.000 VH3-21 VL1-40 0 2

ADI-24843 Unknown 0.039 VH4-304 VK4-1 0 0

ADI-24845 Site III 0.000 VH3-21 VL2-14 0 0

ADI-24846 Unknown 0.000 VH3-21 VL1-47 0 0

ADI-24847 Unknown 0.012 VH3-21 VL1-40 1 0

ADI-24848 Site V 0.644 VH3-21 VL1-40 0 0

ADI-24849 Site 0 0.741 VH3-43 VK1-33 2 0

ADI-24850 Site III 0.574 VH3-21 VL1-40 0 0

ADI-24851 Site I 0.675 VH1-2 VL2-8 0 0

ADI-24852 Site IV 0.277 VH1-3 VL3-1 1 2

ADI-24854 Unknown 0.658 VH3-21 VL1-40 0 0

ADI-24855 Site III 0.600 VH3-21 VL1-40 0 0

ADI-24856 Site I 0.101 VH1-18 VK3-20 0 0

ADI-24857 Site III 0.000 VH3-21 VL1-40 0 0

ADI-24858 Site III 0.119 VH3-21 VL1-40 0 0

ADI-24859 Site III 0.000 VH3-21 VL1-40 0 0

ADI-24860 Site III 0.000 VH3-11 VL1-40 4 2

ADI-24861 Site III 0.000 VH3-21 VL1-40 2 0

ADI-24862 Unknown 0.000 VH4-31 VL3-1 0 0

ADI-24863 Site III 0.000 VH3-21 VL1-40 1 0

ADI-19467 Site III 0.010 VH3-21 VL1-40 0 0

ADI-19468 Site I 0.000 VH4-39 VL6-57 0 0

ADI-19469 Site I 0.143 VH4-b VK3-11 0 0

ADI-19470 Site II 0.110 VH3-30 VL3-1 0 0

ADI-19471 Unknown 0.040 VH3-64 VL6-57 0 0

ADI-19473 Site I 0.063 VH5-51 VL6-57 0 0

ADI-19474 Site I 0.032 VH5-51 VL6-57 0 0

ADI-19475 Site V 0.000 VH1-18 VK2-30 10 2

ADI-19476 Unknown 0.093 VH2-5 VL2-11 2 3

ADI-19478 Unknown 0.033 VH4-39 VL1-36 5 2

ADI-19479 Unknown 0.012 VH1-69 VK2-30 2 3

ADI-19480 Site IV 0.012 VH3-21 VL6-57 6 3

ADI-19481 Unknown 0.000 VH3-43 VK1-39 1 3

ADI-19482 Site II 0.159 VH4-34 VK1-5 11 1

ADI-19483 Site IV 0.050 VH5-51 VL6-57 4 2

ADI-19484 Unknown 0.000 VH4-30 VK1-39 5 2

ADI-19485 Site I 0.039 VH4-31 VK3-15 11 3

ADI-19486 Site I 0.006 VH4-59 VL2-14 5 0

ADI-19487 Unknown 0.104 VH2-70 VK1-39 3 0

ADI-19488 Unknown 0.000 VH1-24 VK2-28 0 0

ADI-19489 Site IV 0.000 VH2-70 VK1-17 2 0

ADI-19490 Unknown 0.000 VH3-15 VK2-28 0 0

ADI-19491 Unknown 0.000 VH2-5 VL1-40 0 0

ADI-19492 Site IV 0.034 VH5-51 VL6-57 1 2

ADI-19493 Site I 0.037 VH4-34 VL3-1 0 0

ADI-19494 Site 0 0.065 VH1-69 VL2-14 4 1

ADI-19495 Unknown 0.047 VH4-59 VK1-12 0 0

ADI-19496 Unknown 0.000 VH3-30 VK4-1 1 1

ADI-19497 Site I 0.002 VH1-46 VL6-57 0 0

ADI-19498 Site I 0.045 VH3-66 VL3-25 1 0

ADI-19499 Site I 0.089 VH4-39 VL6-57 0 0

ADI-19500 Unknown 0.000 VH3-48 VK1-8 0 0

ADI-19501 Site V 0.000 VH1-18 VK2-30 6 2

ADI-19502 Unknown 0.000 VH3-30 VK4-1 5 2

ADI-19503 Site I 0.040 VH1-46 VL3-10 0 0

ADI-19505 Site IV 0.039 VH5-51 VL3-9 5 1

ADI-22756 Unknown 0.171 VH3-30 VK3-20 6 4

ADI-22757 Site V 0.000 VH1-18 VK2-30 7 4

ADI-22758 Site III 0.000 VH3-21 VL1-40 5 3

ADI-22759 Site III 0.018 VH3-21 VL1-40 9 3

ADI-22760 Site II 0.000 VH3-9 VL1-47 5 4

ADI-22762 Site I 0.000 VH6-1 VL1-40 7 4

ADI-22763 Site I 0.000 VH3-48 VK1-39 9 3

ADI-22764 Site I 0.336 VH4-4 VK1-39 5 12

ADI-22765 Site V 0.000 VH3-21 VL1-40 0 0

ADI-22766 Unknown 0.000 VH3-9 VL2-8 0 1

ADI-22767 Site III 0.033 VH3-21 VL1-40 0 0

ADI-22768 Site I 0.000 VH3-48 VK1-39 0 0

ADI-22769 Unknown 0.011 VH3-72 VL3-1 0 0

ADI-22770 Unknown 0.004 VH2-70 VL3-1 0 0

ADI-22771 Site III 0.010 VH3-21 VL1-40 0 0

ADI-22772 Unknown 0.000 VH3-30 VL3-1 0 0

ADI-22773 Site V 0.000 VH1-18 VK2-30 0 0

ADI-22774 Site III 0.000 VH3-21 VL1-40 0 4

ADI-22775 Unknown 0.000 VH3-33 VK1-12 4 2

ADI-22776 Unknown 0.000 VH3-11 VL3-21 0 0

ADI-22777 Site II 0.000 VH1-02 VL3-01 12 13

ADI-22778 Site I 0.109 VH4-59 VK1-39 12 7

ADI-22779 Site I 0.000 VH4-34 VK1-39 7 8

ADI-22780 Site III 0.004 VH4-31 VL2-14 0 2

ADI-22781 Site I 0.033 VH3-48 VL3-01 0 0

ADI-14333 Site III 0.046 VH3-21 VL1-40 7 4

ADI-14334 Site III 0.005 VH3-21 VL1-40 14 4

ADI-14335 Site IV 0.000 VH3-49 VK1-39 4 6

ADI-14336 Site V 0.005 VH1-18 VK2-30 4 5

ADI-14337 Site III 0.000 VH3-21 VL1-40 0 0

ADI-14338 Site I 0.000 VH3-30 VK1-39 13 3

ADI-14339 Site IV 0.040 VH3-30 VL3-25 14 4

ADI-14340 Site 0 0.050 VH3-21 VL3-21 7 5

ADI-14341 Unknown 0.111 VH3-48 VK1-5 7 1

ADI-14342 Site I 0.000 VH2-26 VK1-39 3 6

ADI-14343 Site I 0.003 VH1-69 VK2-28 8 5

ADI-14344 Unknown 0.113 VH3-23 VL3-1 8 7

ADI-14345 Site IV 0.059 VH1-24 VK1-39 9 1

ADI-14346 Site III 0.102 VH3-21 VL1-40 8 1

ADI-14347 Site III 0.040 VH3-21 VL1-40 6 1

ADI-14348 Site I 0.105 VH3-30 VL2-11 10 5

ADI-14349 Unknown 0.000 VH1-69 VK4-1 9 3

ADI-14350 Site II 0.027 VH4-61 VL1-40 13 2

ADI-14351 Site IV 0.027 VH3-74 VL3-21 9 3

ADI-14352 Unknown 0.142 VH4-304 VK3-20 5 3

ADI-14353 Site I 0.051 VH1-69 VL2-14 10 4

ADI-14354 Site I 0.069 VH1-69 VL2-14 8 6

ADI-14355 Site IV 0.038 VH2-5 VL2-14 4 7

ADI-14356 Site I 0.034 VH4-34 VL3-25 0 0

ADI-14357 Unknown 0.000 VH3-30 VK1-39 5 4

ADI-14358 Site I 0.103 VH3-11 VL2-14 7 12

ADI-14359 Site I 0.000 VH2-70 VK1-39 1 0

ADI-14360 Site IV 0.000 VH1-3 VK2-28 2 0

ADI-14361 Unknown 0.068 VH3-23 VL1-40 14 7

ADI-14362 Site I 0.389 VH3-23 VK1-39 2 1

ADI-14363 Site IV 0.000 VH3-11 VK3-20 6 4

ADI-14364 Site 0 0.104 VH5-51 VL3-21 3 0

ADI-14365 Site IV 0.000 VH1-24 VK1-39 8 4

ADI-14366 Unknown 0.000 VH1-18 VK1-39 8 8

ADI-14367 Unknown 0.000 VH3-23 VK3-20 10 2

ADI-14368 Site II 0.106 VH3-15 VL3-21 4 6

ADI-14369 Unknown 0.059 VH1-69 VL1-44 6 6

ADI-14370 Unknown 0.726 VH3-30 VL2-8 6 0

ADI-14371 Unknown 0.000 VH3-23 VK1-39 10 8

ADI-14372 Unknown 0.000 VH3-23 VK1-6 11 3

ADI-14373 Site I 0.000 VH4-34 VK3-15 4 0

ADI-14374 Unknown 0.103 VH3-43 VL3-21 6 13

ADI-14375 Unknown 0.019 VH3-23 VL1-40 10 6

ADI-14376 Site I 0.085 VH3-74 VL3-10 7 3

ADI-14377 Unknown 0.000 VH3-30 VK1-17 5 0

ADI-14378 Unknown 0.000 VH3-74 VK1-39 3 3

ADI-14379 Unknown 0.487 VH3-30 VL3-1 5 11

ADI-14380 Unknown 0.102 VH5-51 VL1-51 5 2

ADI-14381 Site I 0.009 VH3-48 VK1-6 7 1

ADI-14382 Site I 0.118 VH3-33 VL2-14 8 5

ADI-14383 Site II 0.100 VH2-5 VL2-23 6 4

ADI-14384 Site I 0.062 VH4-30 VL3-21 7 7

ADI-14385 Site I 0.028 VH5-51 VL6-57 0 1

ADI-14386 Site I 0.070 VH3-23 VL3-1 6 7

ADI-14388 Unknown 0.147 VH3-30 VL7-43 2 4

ADI-14389 Site I 0.181 VH3-15 VK1-39 12 6

ADI-14390 Unknown 0.129 VH4-b VL2-23 1 3

ADI-14391 Unknown 0.033 VH3-23 VL3-10 11 4

ADI-14392 Unknown 0.000 VH1-69 VK3-11 2 0

ADI-14393 Site III 0.199 VH3-21 VL1-40 14 4

ADI-14394 Site III 0.038 VH3-21 VL1-40 0 0

ADI-14395 Site IV 0.128 VH3-30 VK1-5 0 0

ADI-14396 Unknown 0.000 VH3-30 VK1-33 0 0

ADI-14397 Site IV 0.120 VH3-30 VK1-5 0 0

ADI-14399 Unknown 0.004 VH4-304 VK3-11 7 4

ADI-14400 Unknown 0.000 VH3-30 VK1-6 8 1

ADI-14401 Site III 0.005 VH3-21 VL1-40 9 4

ADI-14402 Site V 0.000 VH1-18 VK2-30 3 2

ADI-14403 Site III 0.010 VH3-11 VL1-40 7 4

ADI-14404 Unknown 0.037 VH3-48 VK1-5 7 5

ADI-14405 Site IV 0.031 VH1-18 VL3-21 11 5

ADI-14406 Site I 0.060 VH5-51 VK2-28 10 1

ADI-14407 Site I 0.000 VH3-33 VK1-39 5 7

ADI-14408 Site I 0.000 VH2-70 VK1-39 5 5

ADI-14409 Unknown 0.014 VH1-18 VK4-1 6 4

ADI-14410 Unknown 0.101 VH4-34 VL1-47 8 6

ADI-14411 Unknown 0.047 VH1-46 VK1-39 7 5

ADI-14412 Site IV 0.000 VH1-18 VK3-20 9 5

ADI-14413 Unknown 0.028 VH3-43 VL1-44 9 6

ADI-14414 Unknown 0.109 VH1-69 VK3-11 15 7

ADI-14415 Unknown 0.000 VH4-59 VK1-9 7 5

ADI-14416 Site IV 0.053 VH5-51 VL6-57 23 5

ADI-14417 Unknown 0.297 VH3-21 VK3-15 9 3

ADI-14418 Site II 0.000 VH1-69 VK1-5 10 3

ADI-14419 Unknown 0.325 VH3-30 VK3-20 9 1

ADI-14420 Site IV 0.000 VH3-43 VK1-5 4 3

ADI-14421 Unknown 0.055 VH5-51 VK3-15 20 2

ADI-14422 Site I 0.000 VH1-69 VL1-40 1 0

ADI-14423 Unknown 0.000 VH3-43 VK1-17 7 0

ADI-14424 Site II 0.051 VH5-51 VL6-57 16 9

ADI-14425 Site I 0.027 VH4-61 VL2-14 5 2

ADI-14426 Site I 0.072 VH3-30 VL3-19 8 5

ADI-14427 Site I 0.108 VH1-69 VL2-11 9 1

ADI-14428 Unknown 0.110 VH3-11 VL3-21 4 2

ADI-14654 Unknown 0.106 VH1-69 VL3-19 10 5

ADI-14655 Site I 0.000 VH3-15 VK1-39 0 0

ADI-14656 Site I 0.050 VH3-30 VL3-19 8 5

ADI-14657 Site IV 0.000 VH1-18 VK1-27 9 1

ADI-14658 Site I 0.040 VH3-33 VL2-14 0 1

ADI-14659 Unknown 0.000 VH3-11 VK3-20 9 10

ADI-14571 Unknown 0.000 VH1-69 VK1-9 10 1

ADI-14572 Unknown 0.148 VH3-15 VL1-44 4 3

ADI-14573 Unknown 0.031 VH1-18 VL3-21 7 3

ADI-14575 Site I 0.096 VH1-69 VL2-14 0 1

ADI-14576 Site V 0.000 VH1-18 VK2-30 0 0

ADI-14577 Site V 0.000 VH1-18 VK2-30 11 3

ADI-14578 Unknown 0.120 VH1-69 VL1-51 6 6

ADI-14579 Site I 0.117 VH5-51 VK1-27 2 0

ADI-14580 Unknown 0.000 VH1-69 VK4-1 12 3

ADI-14581 Unknown 0.000 VH1-69 VK3-15 13 3

ADI-14582 Site II 0.104 VH5-51 VL6-57 15 8

ADI-14583 Site V 0.000 VH1-18 VK2-30 10 4

ADI-14584 Unknown 0.000 VH1-18 VK1-39 20 2

ADI-14585 Site V 0.000 VH1-18 VK2-30 5 5

ADI-14586 Site III 0.000 VH3-11 VL1-40 0 0

ADI-14587 Site III 0.010 VH3-21 VL1-40 3 2

ADI-14588 Site IV 0.000 VH1-24 VK1-39 9 2

ADI-14589 Site I 0.000 VH2-26 VK1-39 6 8

ADI-14590 Site II 0.000 VH5-51 VK1-13 3 2

ADI-14591 Unknown 0.116 VH5-a VK1-39 7 4

ADI-14592 Site IV 0.083 VH5-51 VL6-57 12 4

ADI-14593 Site IV 0.017 VH5-51 VL6-57 7 4

ADI-14594 Unknown 0.030 VH1-18 VL3-21 10 2

ADI-14595 Site I 0.101 VH3-48 VK3-11 10 5

ADI-14596 Unknown 0.052 VH3-23 VK1-39 2 0

ADI-14597 Site IV 0.000 VH3-43 VK3-20 6 1

ADI-14598 Site I 0.000 VH1-69 VK1-27 8 1

ADI-14599 Site IV 0.092 VH3-49 VL6-57 7 2

ADI-14600 Site III 0.069 VH3-11 VL1-40 3 1

ADI-14601 Unknown 0.045 VH3-23 VK1-12 5 5

ADI-14602 Site IV 0.114 VH3-30 VL3-1 6 5

ADI-14603 Unknown 0.036 VH5-51 VK1-27 6 4

ADI-14604 Unknown 0.110 VH3-23 VL1-44 11 7

ADI-14605 Unknown 0.103 VH2-70 VL3-25 5 6

ADI-14606 Unknown 0.000 VH3-66 VK3-15 4 5

ADI-14607 Site IV 0.075 VH3-30 VL3-25 10 8

ADI-20959 Site V 0.000 VH1-18 VK2-30 7 5

ADI-20960 Site II 0.102 VH4-34 VK1-5 14 7

ADI-20961 Site III 0.059 VH3-21 VL1-40 20 5

ADI-20962 Site V 0.000 VH1-18 VK2-30 10 2

ADI-20963 Site I 0.051 VH3-21 VL3-21 17 9

ADI-20964 Site V 0.000 VH1-18 VK2-30 4 2

ADI-20965 site IV 0.109 VH1-18 VL3-21 11 6

ADI-20966 Site III 0.035 VH3-21 VL1-40 20 8

ADI-20967 Site I 0.000 VH3-30 VK2-28 11 1

ADI-20968 site IV 0.000 VH4-34 VK1-33 11 10

ADI-20969 Site III 0.094 VH3-21 VL1-40 13 6

ADI-20970 Unknown 0.000 VH3-15 VK1-33 3 5

ADI-20971 Site I 0.000 VH3-21 VK3-15 20 7

ADI-20972 Site I 0.103 VH4-34 VL2-14 13 5

ADI-20973 Site III 0.096 VH3-21 VL1-40 13 6

ADI-20974 Site III 0.107 VH3-21 VL1-40 18 6

ADI-20975 site IV 0.028 VH1-18 VL3-21 20 8

ADI-20976 Site I 0.000 VH3-23 VK1-39 33 10

ADI-20977 Unknown 0.000 VH3-23 VK3-20 3 1

ADI-20978 Site V 0.000 VH1-18 VK2-30 8 1

ADI-20979 Site 0 0.034 VH4-59 VL2-14 8 5

ADI-20980 Unknown 0.000 VH4-61 VK3-11 9 7

ADI-20981 Unknown 0.352 VH4-304 VK1-12 18 8

ADI-20982 Unknown 0.000 VH4-61 VK1-5 15 7

ADI-20983 Site I 0.000 VH3-64 VK1-33 13 5

ADI-20984 Site IV 0.026 VH1-24 VK1-39 23 32

ADI-20986 Site 0 0.000 VH3-7 VK3-20 9 6

ADI-20987 Unknown 0.000 VH3-33 VK3-20 7 2

ADI-20988 Site V 0.000 VH1-18 VK2-30 12 3

ADI-20989 Site I 0.000 VH4-4 VK1-39 9 9

ADI-20990 Site I 0.000 VH3-30 VK2-28 16 4

ADI-20991 Site III 0.022 VH3-11 VL1-40 8 2

ADI-20992 Site V 0.000 VH3-7 VK1-39 9 6

ADI-20993 Site I 0.135 VH3-30 VK2-28 13 7

ADI-20994 site IV 0.020 VH1-18 VL3-21 16 3

ADI-20995 Unknown 0.000 VH5-51 N/A 9 0

ADI-20996 Site I 0.015 VH2-70 VK1-39 3 8

ADI-20997 Site I 0.000 VH3-30 VK3-20 14 9

ADI-20998 Site 0 0.109 VH3-30 VL2-11 9 5

ADI-20999 Unknown 0.088 VH4-39 VL1-51 15 5

ADI-21000 Site I 0.000 VH2-26 VK1-39 12 4

ADI-21001 Site IV 0.000 VH4-39 VK4-1 10 1

ADI-21002 Site I 0.010 VH4-4 VK1-39 16 7

ADI-21003 Site IV 0.000 VH4-34 VK2-28 4 2

ADI-21004 Site IV 0.000 VH3-33 VK4-1 8 12

ADI-21005 Unknown 0.000 VH3-43 VK3-20 16 6

ADI-21006 Site III 0.000 VH2-5 VK2-30 6 8

ADI-21007 Site IV 0.082 VH1-46 VL6-57 12 3

ADI-21008 Site I 0.000 VH4-34 VK3-11 15 2

ADI-21009 Unknown 0.040 VH1-18 VL2-23 20 9

ADI-21010 Site III 0.000 VH3-33 VK1-5 15 6

ADI-21011 Site I 0.109 VH4-59 VK1-39 23 9

ADI-21012 Site I 0.018 VH2-70 VK1-39 7 7

ADI-21013 Site V 0.000 VH4-39 VK3-20 13 6

ADI-21014 Site 0 0.112 VH4-59 VK1-33 24 10

ADI-21015 Site IV 0.000 VH1-24 VK1-39 15 4

ADI-21017 Site V 0.000 VH1-18 VK2-30 8 4

ADI-21018 Site III 0.031 VH3-21 VL1-40 8 5

ADI-21019 Site IV 0.000 VH3-23 VK2-28 15 3

ADI-21021 Site IV 0.000 VH4-34 VK1-5 10 11

ADI-21022 Unknown 0.003 VH4-59 VL3-21 8 3

ADI-21023 Site III 0.060 VH3-21 VL1-40 16 8

ADI-21025 Site III 0.033 VH3-21 VL1-40 11 4

ADI-21026 Site I 0.225 VH4-31 VK4-1 9 7

ADI-21027 Site III 0.008 VH4-4 VL1-40 15 5

ADI-21028 Unknown 0.000 VH3-11 VK1-5 10 10

ADI-21029 Unknown 0.000 VH5-51 VK1-39 14 3

ADI-21030 Site III 0.060 VH3-11 VL1-40 12 8

ADI-21031 Unknown 0.004 VH4-61 VK3-11 21 7

ADI-21032 Site III 0.054 VH3-21 VL1-40 14 5

ADI-21033 Site 0 0.000 VH5-51 VK1-33 20 8

ADI-21034 Site I 0.015 VH5-a VK3-20 11 5

ADI-21035 Site I 0.033 VH1-18 VK1-5 14 8

ADI-21036 Site I 0.101 VH5-51 VL2-23 16 16

ADI-21037 Site I 0.122 VH3-30 VK2-28 13 4

ADI-21038 Site I 0.000 VH5-51 VK3-20 15 1

ADI-21039 Site I 0.102 VH1-46 VK2-28 11 0

ADI-21040 Unknown 0.046 VH4-4 VL1-40 14 6

ADI-21041 Unknown 0.000 VH3-43 VK1-39 3 3

ADI-21042 Site I 0.000 VH4-31 VK1-5 18 7

ADI-21043 Site I 0.059 VH1-18 VL3-21 8 4

ADI-21044 Unknown 0.000 VH5-51 VK1-39 16 6

ADI-21045 Site III 0.032 VH3-21 VL1-40 18 5

ADI-21046 Site IV 0.089 VH5-51 VL1-40 16 7

ADI-21047 Site IV 0.000 VH4-34 VK1-33 14 4

ADI-21048 site IV 0.087 VH1-18 VL3-21 8 3

ADI-21049 Site III 0.102 VH3-21 VL1-40 7 3

ADI-21050 Site V 0.000 VH1-18 VK2-30 10 7

ADI-21051 Unknown 0.000 VH4-61 VK3-11 14 6

ADI-21052 site IV 0.085 VH1-18 VL3-21 2 3

ADI-21053 Site I 0.027 VH4-31 VK1-39 37 1

ADI-21054 Site IV 0.000 VH3-30 VK1-5 21 9

ADI-21055 Site I 0.110 VH3-33 VL1-44 12 10

ADI-21056 Site III 0.020 VH3-21 VL1-40 15 6

ADI-21057 Site 0 0.000 VH5-51 VK3-15 13 1

ADI-21058 Site III 0.000 VH4-304 VK3-15 20 3

ADI-21059 Unknown 0.000 VH5-51 VK1-39 14 8

ADI-21060 Site III 0.105 VH3-11 VL1-40 26 6

ADI-21061 Site I 0.084 VH1-69 VL2-14 22 8

ADI-21062 Site I 0.000 VH3-21 VK1-39 20 9

ADI-21063 Site V 0.000 VH3-64 VK1-39 7 3

ADI-21064 Site V 0.000 VH1-18 VK2-30 16 3

ADI-21065 Unknown 0.000 VH3-23 VK3-20 7 2

ADI-21067 Site IV 0.000 VH4-34 N/A 11 0

ADI-21068 Site III 0.021 VH4-4 VL1-40 19 3

ADI-21069 site IV 0.000 VH1-18 VL3-21 16 5

ADI-21070 Site II 0.000 VH3-23 VK3-15 12 3

ADI-21071 Site I 0.019 VH3-33 VK1-39 14 7

ADI-21072 Site III 0.010 VH3-21 VL1-40 16 3

ADI-21073 Site I 0.000 VH3-48 VK1-39 18 8

ADI-21075 Site III 0.021 VH3-21 VL1-40 17 2

ADI-21076 Site III 0.015 VH3-21 VL1-40 16 7

ADI-21077 Site III 0.018 VH3-11 VL1-40 9 2

ADI-21078 Site III 0.017 VH3-11 VL1-40 10 5

ADI-21079 Site III 0.064 VH3-11 VL1-40 5 1

ADI-21080 Site III 0.006 VH3-11 VL1-40 16 2

ADI-21081 Site III 0.031 VH3-11 VL1-40 12 5

ADI-21082 Site III 0.004 VH3-21 VL1-40 13 5

ADI-21083 Site 0 0.101 VH4-4 VL2-11 12 6

ADI-21084 site IV 0.100 VH1-18 VL3-21 19 6

ADI-21085 Site III 0.167 VH3-21 VL1-40 9 6

ADI-21086 Site III 0.024 VH3-11 VL1-40 16 4

ADI-21087 Unknown 0.000 VH3-48 VK1-5 7 1

ADI-21089 Site III 0.065 VH3-21 VL1-40 11 3

ADI-21090 Site IV 0.000 VH3-11 VK3-15 28 6

ADI-21091 Site I 0.005 VH5-a VL1-51 13 6

Analysis of the relationship between binding affinity and neutralization potency demonstrated that the majority of highly potent neutralizing antibodies bound with high apparent affinity to preF (K D <1.0 nM) and failed to bind to postF ( FIG. 3 D ). In addition, although approximately 20% of the neutralizing antibodies isolated from infants ≥6 mo. recognized both preF and postF, this type of neutralizing antibody was very rare in infants <3 mo. ( FIGS. 3 D and 4 B ), demonstrating that nearly all neutralizing antibodies in very young infants are preF-specific.

Next, the polyreactivity of the infant antibodies was assessed using a previously described assay (Jain et al., 2017; Kelly et al., 2015; Xu et al., 2013). Although the fraction of medium-to-highly polyreactive antibodies was relatively low (≤15%) for all infants, there was a higher frequency of polyreactive antibodies in the infants <3 mo. compared to the infants ≥6 mo. ( FIG. 5 A ). This result could be related to differences in tolerance mechanisms in these two infant populations or to the higher frequency of antibodies containing little to no SHM in the younger infants. In support of the latter hypothesis, stratification of the antibodies based on their SHM levels showed that 12% of antibodies that lacked SHM displayed medium-to-high levels of polyreactivity, compared with only 2% of antibodies that contained >5 VH gene substitutions ( FIG. 5 B ). This result is consistent with a prior study showing that the process of affinity maturation can result in decreased polyreactivity of human antibodies (Reed et al., 2016).

Infant Antibody Responses are Focused Primarily on Two Antigenic Sites that have Different Neutralization Sensitivity

To define the epitopes targeted by the infant antibodies, each antibody was tested for competition with other known RSV F-specific antibodies and assigned to an antigenic site based on the resulting competition profile ( FIGS. 6 A and 6 B ). In the three youngest infants, responses were dominated by antibodies directed against site III, whereas in the other infants, a larger proportion of the responses were directed against site I, and in some cases site IV ( FIG. 6 B ). The proportion of antibodies recognizing preF-specific sites Ø and V at the apex of the preF molecule was low, particularly in the three youngest infants. Interestingly, analysis of the VH and VL germline gene usage for the site I-directed antibodies revealed that over 25% of the antibodies that recognized site I utilized the VK1-39 light chain gene ( FIG. 7 A ). Although these site I-directed antibodies utilized a variety of VH genes, many possessed a convergent CDR H3 motif, generated from recombination of the DH3-22 and JH-4 genes ( FIG. 7 C ). In contrast, nearly 85% of antibodies that recognized site III utilized either the VH3-21/VL1-40 or the related VH3-11/VL1-40 germline gene pairing ( FIG. 7 B ) and did not show evidence of a convergent CDR H3 sequence.

The majority of site III-directed antibodies were preF-specific and neutralizing, whereas antibodies that recognized site I preferentially bound to postF and tended to be weak or non-neutralizing ( FIGS. 6 C, 7 D, and 7 E ). In infants <3 mo., 60% of antibodies that displayed highly potent neutralizing activity (IC 50 <0.05 ug/ml) were directed against site III ( FIG. 6 C ). Therefore, although antibodies against both sites I and III are readily elicited during natural RSV infection in infants, site III-directed antibodies can potently neutralize RSV whereas site I-directed antibodies are typically non-neutralizing.

Site III-Directed Antibodies can Potently Neutralize RSV in the Absence of SHM and are Present in the Naïve B Cell Repertoire

Next, the epitope specificities of the neutralizing antibodies that lacked SHM were analyzed ( FIG. 8 A ). Of the 33 germline antibodies that displayed RSV-neutralizing activity, 27 targeted antigenic site III. Analysis of the index sort data revealed that approximately half of these antibodies originated from naïve b cells (IgG − IgA − CD27 − ) and the other half originated from memory B cells that expressed IgG, IgA, or CD27 ( FIG. 8 B ). The identification of neutralizing site III-directed antibodies from B cells that lacked both SHM and classical memory B cell markers led to an investigation of the occurrence of these antibody specificities in the naïve B cell repertoire. Therefore, 112 and 19 antibodies from RSV F-reactive cord blood B cells and adult naïve B cells, respectively, were cloned and expressed. Due to the low affinity of naïve B cell-derived antibodies, only 22/112 (20%) antibodies sorted from cord blood and 9/19 (47%) antibodies from adult naïve B cells bound with measurable affinity to RSV F as full-length IgGs. However, 11/22 (50%) and 7/9 (78%) of the RSV F binding antibodies from cord blood and adult naïve B cells, respectively, utilized VH3-21/VL1-40 or VH3-11/VL1-40 germline gene pairing ( FIG. 8 C ). Of these 18 antibodies, the 13 with binding affinities that allowed for analysis in a competition assay were all shown to recognize antigenic site III (Table 3). Antibodies derived from naïve B cells isolated from cord blood or the PMBCs of healthy adults were tested for competition with three control IgGs and displayed profiles consistent with recognition of antigenic site III. Results are expressed as the fold reduction in antigen binding in the presence of saturating concentrations of competitor Fab relative to an antigen-only control. N.D.; not determined due to low binding affinity.

TABLE 3

Naïve B cells that utilize the VH3-21/VL1-40

and VH3-11/VL1-40 gene pairs recognize site III

Competitor Fab

D25 MPE8 Motavizumab

(Antigenic site ∅) (Antigenic site III) (Antigenic site II)

Control D25 153 1 1

IgGs MPE8 1 228 20

Motavizumab 1 1 39

IgGs derived ADI-32365 8 11 19

from naïve ADI-28517 11 23 55

B cells ADI-32361 7 50 169

ADI-32367 7 13 35

ADI-31917 3 69 190

ADI-31918 2 11 30

ADI-31919 1 55 159

ADI-28537 3 52 156

ADI-31921 3 37 112

ADI-32360 2 128 416

ADI-32362 3 117 370

ADI-32363 2 176 537

ADI-32366 3 61 10

ADI-28522 N.D. N.D. N.D.

ADI-31920 N.D. N.D. N.D.

ADI-28523 N.D. N.D. N.D.

ADI-28526 N.D. N.D. N.D.

ADI-28527 N.D. N.D. N.D.

The apparent binding affinities of these antibodies for preF were relatively high, ranging from 1.0-60 nM ( FIG. 8 C ). In addition, approximately 40% of these site-III directed antibodies displayed neutralizing activity, with IC 50 s ranging from 1.5-4.0 μg/mL ( FIG. 8 C ). In contrast, none of the naïve B cell-derived antibodies that utilized other germline gene combinations showed detectible neutralizing activity ( FIG. 8 C ). Collectively, these results indicate that site III-directed antibodies can neutralize RSV in the absence of SHM and that these types of antibodies are present in the naïve B cell repertoire.

A Site I-Directed Non-Neutralizing Antibody Recognizes postF Using a Convergent CDR H3 Motif and Germline-Encoded Regions of the VK1-39 Light Chain

The structure of a site I-directed antibody, ADI-14359, in complex with postF was characterized to define the molecular determinants of the convergent antibody features ( FIG. 9 A ) (Table 4).

TABLE 4

Crystallographic data collection and refinement statistics

Prefusion RSV F +

Postfusion RSV F + ADI-19425 ADI-19425 Fab +

ADI-14359 Fab Fab AM22 Fab

PDB ID 6APB 6APC 6APD

Data collection

Space group P2 1 2 1 2 1 P2 1 2 1 2 1 P4 1 2 1 2

Cell constants

a, b, c (Å) 88.5, 99.0, 323.3 61.2, 66.5, 126.0 229.5, 229.5, 304.1

α, β, γ (°) 90, 90, 90 90, 90, 90 90, 90, 90

Wavelength (Å) 1.1809 0.9792 0.9793

Resolution (Å) 51.1-3.0 (3.08-3.00) 26.1-1.7 (1.73-1.70) 50.9-4.1 (4.20-4.10)

Unique reflections 57,978 (4,439) 57,347 (2,940) 64,175 (4,439)

R merge 0.449 (1.662) 0.069 (0.328) 0.364 (1.545)

R pim 0.177 (0.650) 0.028 (0.153) 0.108 (0.443)

I/σI 5.2 (1.6) 16.8 (4.2) 6.3 (1.9)

CC 1/2 0.952 (0.564) 0.998 (0.930) 0.995 (0.609)

Completeness (%) 100.0 (100.0) 99.9 (99.4) 99.9 (100.0)

Redundancy 7.3 (7.4) 6.8 (5.5) 12.2 (13.0)

Wilson B-factors 11.5 29.4 117.9

Refinement

Resolution (Å) 51.1-3.0 (3.05-3.00) 26.1-1.7 (1.73-1.70) 50.9-4.1 (4.16-4.10)

Unique reflections 57,820 (2,724) 57,181 (2,645) 64,084 (2,497)

R work /R free (%) 22.0/25.3 17.4/20.4 20.9/26.1

No. atoms

Protein 13,264 3,233 30,005

Ligand/ion 42 10 —

Water — 692 —

B-factors

Protein 37.2 15.9 167.2

Ligand/ion 76.5 21.3 —

Water — 30.2 —

R.m.s. deviations

Bond lengths (Å) 0.004 0.003 0.003

Bond angles (°) 0.91 0.667 0.632

Ramachandran

Favored (%) 95.9 97.5 95.1

Allowed (%) 3.8 2.1 4.7

Outliers (%) 0.4 0.5 0.2

Values in parentheses are for the highest-resolution shell.

The structure revealed that the CDR H3, generated from the convergent usage of DH3-22/JH-4, is inserted into a small groove near the top of the postF trimer ( FIG. 9 B ) and makes a number of hydrogen bonds with postF residues in and around this groove ( FIG. 9 C ). CDR H3 residues Tyr100c and Tyr100d (Kabat numbering), which are uncommon in D genes other than DH3-22, form hydrogen bonds with postF residues Glu31 and Glu378, respectively, which are located on the ridge surrounding the site I groove. The tip of the CDR H3 loop is composed of three small amino acids that allow the loop to fit into the groove and make hydrogen bonds with residues Lys42, Asp344, and Asn380 of postF. These small residues also allow the CDR H3 to stack against Trp314, which is positioned at the floor of the groove. In addition, ADI-14359 heavy chain residue Tyr100g, which is unique to the JH4 gene, stacks against Tyr49 in the light chain, which may help properly orient the CDR H3.

Antibodies that utilized this convergent CDR H3 also showed a strong bias towards pairing with the VK1-39 light chain gene. Several germline-encoded residues within CDR L1 and the framework region 3 of VK1-39 form hydrogen bonds with Glu31 on postF ( FIG. 9 C ). In addition, Tyr92 at the start of the CDR L3 is a unique feature of VK1-39, and forms a hydrogen bond with Ser35 on the F2 subunit of postF. The light chain of ADI-14359 is predicted to clash substantially with β22 of preF, which rearranges during the transition to postF to allow formation of the six-helix bundle ( FIG. 10 ). Therefore, preferential binding to postF by this type of antibody is mediated by the light chain.

Although site I-directed antibodies did not show convergent VH gene usage, the heavy chain utilized by ADI-14359 also makes critical interactions with postF ( FIG. 9 C ). The only residue that is mutated from germline in ADI-14359, Arg50, forms a salt bridge with Asp52 in the CDR H2 and appears to assist in coordinating the electrostatic interaction between Asp52, Asp56 and Asp58 of the CDR H2 with Lys390 on postF. Arg50 also forms a hydrogen bond with light chain residue Tyr96, a residue that is unique to the IGK-J2 gene utilized by ADI-14359. To investigate the contribution of these VH gene-mediated interactions to binding, the binding affinity of ADI-14359 Fab and the germline reverted variant (R50L) to postF was measured using surface plasmon resonance (SPR). This analysis revealed that the affinity of the germline reverted variant was reduced by more than 30-fold ( FIG. 9 D ). Also, it was found that substitution of Lys390 on postF with alanine (K390A) almost entirely ablated ADI-14359 binding ( FIG. 9 D ). The presence of three acidic residues in the CDR H2 therefore appears to be critical for the interaction of ADI-14359 with postF. However, the contribution of the CDR H2 to binding may vary among other members of this group, since many of the VH germlines utilized lack this acidic motif.

A Site 111-Directed Neutralizing Antibody Utilizes Germline-Encoded Features of the VH3-21 and VL1-40 Genes for High-Affinity Recognition of preF

To investigate the molecular basis of preferential germline gene pairing in antibodies targeting site III, the crystal structure of ADI-19425 bound to a preF-stabilized variant of RSV F (PR-DM) was determined ( FIGS. 11 A and 12 A , Table 4) (Krarup et al., 2015). This antibody, which was isolated from a 2.8-month old infant, showed potent neutralizing activity despite lacking SHM (Table 2, FIG. 12 B ). The structure revealed that the majority of contacts between ADI-19425 and preF are formed by the light chain, particularly Tyr31 in CDR L1 and Tyr91 in CDR L3, both of which contact the loop connecting α6 to α7 ( FIG. 11 B ). Tyr91 is the only residue in the CDR L3 that directly interacts with F, although contacts between Asp94 and Ser96 may play a role in positioning this loop and preventing a steric clash between ADI-19425 and antigenic site II (α6-α7) of RSV F. Consistent with the structural analysis, substitution of Tyr31 or Tyr91 with alanine resulted in greater than 20- or 80-fold reductions in affinity, respectively, as measured by SPR ( FIG. 11 C ).

In addition to the contacts formed by the light chain, CDR H2 contains a stretch of five consecutive serine residues that form a network of hydrogen bonds with Asp310 on β6 of preF. Notably, the VH3-11 germline gene, which has 92% sequence identity with VH3-21, was utilized by site III-directed antibodies at a much lower frequency than VH3-21 (11% compared with 76%). One explanation for this could be the presence of a tyrosine residue directly following the polyserine motif in VH3-21, but not VH3-11. The structure shows that this residue (Tyr56) is buried in a small groove neighboring antigenic site II ( FIG. 11 B ). Consistent with these observations, substitution of Tyr56 with alanine resulted in a more than 150-fold decrease in affinity ( FIG. 11 C ). Interestingly, although the VH3-48 germline gene also contains the polyserine motif and is present in the naïve B cell repertoire at approximately the same frequency as VH3-11 (DeKosky et al., 2013), only a single site III-directed antibody (ADI-19440) that utilizes VH3-48/VL1-40 was isolated (see Table 2).

The structure also shows that Tyr56 of ADI-19425 is buried in a small groove neighboring antigenic site II on preF ( FIG. 11 B ). Consistent with these observations, substitution of Tyr56 with alanine resulted in a more than 150-fold decrease in affinity ( FIG. 11 C ).

In contrast to the clear VH- and VL-specific features highlighted above, there were fewer restrictions on the sequences of the CDR H3s of site III antibodies, and sequence analysis demonstrated that the CDR H3s varied in length, with some preference towards usage of glycine, serine and tyrosine residues at positions 96-100c ( FIG. 7 C ). The structure reveals that although the ADI-19425 CDR H3 buries approximately 250 Å of preF, it does not form hydrogen bonds or salt bridges with either protomer ( FIG. 11 B ). Notably, the cross-neutralizing antibody MPEG, which has recently been structurally characterized (Wen et al., 2017), utilizes the V H 3-21 and V L 1-40 germline gene pair to recognize site III with a binding mode nearly identical to that of ADI-19425, despite substantial differences in the sequences of the two CDR H3s ( FIGS. 12 C and 12 D ). This is consistent with our observation that multiple CDR H3 sequences can be utilized by this family of antibodies to recognize preF.

Discussion

Although RSV causes substantial mortality in infants, little is known about the specificities and functional characteristics of the infant antibody response to natural RSV infection. Here, it is shown that infant antibody responses to RSV F differ substantially from those of healthy adults, not only in affinity and neutralization potency, but also in the patterns of epitope recognition. The infant responses were focused on two major regions of the RSV F trimer—antigenic sites I and III—neither of which are dominant in adult responses (Gilman et al., 2016). These differences were the most extreme in infants under three months of age, with infants older than six months exhibiting responses that began to resemble healthy adults. This observation is consistent with previous studies showing that the infant immune system begins to mature at around six months of age, but does not attain stable, adult-like characteristics until later in life, at around six years of age (IJspeert et al., 2016; Ridings et al., 1998).

The majority of antibodies that recognized antigenic site III utilized the same VH and VL germline gene pairing, but were not restricted in D- and J-gene usage. Importantly, a subset of these antibodies showed potent neutralizing activity despite containing little to no SHM. Approximately half of these antibodies were derived from memory B cells and the other half were derived from B cells that lacked surface expression of CD27, IgG and IgA, suggesting that they originated from naïve B cells.

Recent work has shown that polyclonal IgM antibodies purified from RSV naive infant sera are capable of neutralizing RSV and it was suggested that these antibodies may represent natural anti-RSV antibodies that react with the N- and O-linked glycans present on the RSV surface glycoproteins (Jans et al., 2016). However, unlike natural IgM antibodies—which rely on avidity, typically recognize common surface antigens, and exhibit some degree of polyreactivity (Panda and Ding, 2015)—the site III-directed antibodies described here bind with high affinity in an IgG backbone, specifically recognize an epitope on RSV F that lacks N-linked glycans, and generally show limited polyreactivity, suggesting that they are distinct from previously described natural antibodies. In addition, the presence of this class of antibodies in the memory compartment of older infants and adults indicates that these B cells can be activated in response to antigen exposure and undergo affinity maturation. Similar germline-mediated recognition in the adaptive immune response has also been described for other viral pathogens, including influenza (Ekiert et al., 2009; Kashyap et al., 2008; Sui et al., 2009; Throsby et al., 2008), hepatitis C virus (Bailey et al., 2017) and human cytomegalovirus (Thomson et al., 2008), and for bacterial pathogens such as Staphylococcus aureus (Yeung et al., 2016). The presence of functional germline antibodies in the human antibody repertoire has been proposed to serve as a type of innate humoral response to life-threatening pathogens that are likely to be encountered early in life (Lerner, 2011). The isolation of this class of antibodies from all seven infants studied here, as well as from cord blood B cells, adult naïve B cells, and memory B cells from previously characterized adult donors (Gilman et al., 2016), suggests that the naïve B cell precursors encoding these antibody specificities are likely present in most individuals. The results suggest that expansion of these cells may be a feasible goal for infant vaccination strategies (in contrast to, e.g., certain types of HIV-neutralizing antibodies, whose inferred germline precursors display limited reactivity with native HIV Env antigens only develop in a subset of HIV-1 infected individuals, and require complex vaccination strategies to elicit (Doria-Rose et al., 2010; Gray et al., 2011; Jardine et al., 2016; Sather et al., 2009; Simek et al., 2009; Sok et al., 2016; Yacoob et al., 2016)).

Antibody responses directed specifically against preF are associated with potent neutralization of RSV in human sera (Magro et al., 2012; Ngwuta et al., 2015), and monoclonal antibodies that bind exclusively to preF have been shown to be substantially more potent than antibodies that recognize both preF and postF (Corti et al., 2013; Gilman et al., 2016; Gilman et al., 2015; McLellan et al., 2013; Mousa et al., 2017). Interestingly, neutralizing antibodies that react with both preF and postF were identified in healthy adults and infants over 6 months old, but were almost entirely absent in the youngest infants analyzed here. Although postF antigens are capable of eliciting neutralizing antibodies that also bind to preF, their inability to elicit preF-specific antibodies would likely prove problematic for use in a young infant population. In addition, our results show that a large fraction of the infant antibody response (15-30%) is directed against antigenic site I, which is preferentially expressed on postF. Since antibodies targeting this site generally showed poor neutralizing activity, vaccination with a postF antigens could drive infant antibody responses toward ineffective recognition of RSV F. Recently, it was shown that formalin inactivated RSV (FI-RSV), the preparation that resulted in vaccine-enhanced disease when administered to infants in the 1960s, displays an abundance of postF on the surface of the virus (Killikelly et al., 2016). Although many factors contribute to the development of vaccine-enhanced disease (Acosta et al., 2015), the high abundance of postF on FI-RSV could result in the induction of high levels of site I-directed antibodies and a low fraction of neutralizing antibodies, which are properties previously associated with the formation of immune complexes that contribute to lung pathology in vaccine-enhanced illness (Murphy and Walsh, 1988; Polack et al., 2002).

An age-dependent increase in the response against antigenic sites Ø and V, which are both present near the apex of the preF trimer, was also observed. Although infant antibodies that targeted these epitopes tended to be potently neutralizing, they were present at low abundance in the responses analyzed here, particularly in infants under three months of age. These data suggest that although the presence of site Ø is likely important for generating neutralizing antibody responses later in life, eliciting a neutralizing response in young infants will likely depend on the presentation of antigenic site III. The observed differences in the dominant epitopes targeted by infant and adult responses provides a unique opportunity for prevention strategies that seek to combine passive and active immunization. For example, vaccines could be designed to preferentially elicit site III antibodies, which would not compete for binding with certain second-generation prophylactic antibodies that target antigenic site Ø, such as MEDI8897. In addition, antibodies elicited by a site-III-specific vaccine would not block access to the apex of the preF trimer on infectious virions, allowing the development of neutralizing antibodies directed against antigenic sites in this region to occur during natural RSV infection.

Materials & Methods

Human Subjects

Families of infants were approached at the time of hospitalization for documented RSV infection. At that point a Dartmouth Committee for the Protection of Human Subjects approved consent was signed to obtain 5-10 cc of blood approximately 1 month after discharge from the Children's Hospital at Dartmouth (CHaD). Families were contacted at the planned time for phlebotomy and arrangements made for blood to be drawn either at CHaD or at a medical facility closer to their home.

Plasma Neutralization Titers

Infant plasma samples were tested for RSV neutralization in microtiter assays using an RSV construct containing green fluorescent protein (GFP) and luciferase reporter genes (RSV-GFP1-Luc2, ViraTree). Hep2 cells were added to 96-well plates at a density of 1.8×10 4 cells per well in 100 μL of MEM with 2% FBS/1X penicillin-streptomycin solution (2% MEM) and allowed to adhere overnight at 37° C. On the day of the assay, plasma samples were serially diluted two-fold (1:4 to 1:128,000) in 2% MEM containing RSV-GFP1-Luc2 and incubated for 1 hr at 37° C. Culture media was aspirated from the Hep2 cells followed by the addition of 100 μL/well of the plasma-RSV-GFP1-Luc2 mixture to triplicate wells. Cultures were maintained at 37° C. for 24 hrs and luciferase expression was quantified in cell lysates using the Renilla-Glo® assay system (Promega). Relative light units (RLU) were measured on a BioTek Synergy 2 microplate reader. Neutralization is expressed as the reciprocal of the highest plasma dilution to yield a 60% reduction in RLU as compared to control wells with no added plasma

Production of RSV F Sorting Probes

To generate sorting probes with high avidity, and uniformly oriented F proteins, preF (DS-Cav1) and postF (F ΔFP) trimers with a single biotinylated C-terminal AviTag were produced before coupling to streptavidin-PE or -APC (Gilman et al., 2016).

Single B-Cell Sorting from Infants Less than 3 Months of Age

Peripheral blood mononuclear cells from RSV-infected infants were stained using anti-human IgG (BV605), IgA (FITC), CD27 (BV421), CD8 (PerCP-Cy5.5), CD14 (PerCP-Cy5.5), CD19 (PECy7), CD20 (PECy7) and a mixture of dual-labeled preF and postF tetramers (50 nM each). For naïve B cell sorting, cord blood or peripheral blood mononuclear cells were stained with anti-human IgG (BV605), IgM (FITC), CD27 (BV421), CD8 (PerCP-Cy5.5), CD14 (PerCP-Cy5.5), CD19 (PECy7), CD20 (PECy7) and a mixture of dual-labeled preF and postF tetramers (50 nM each). Tetramers were prepared fresh for each experiment. Single cells were sorted on a BD fluorescence-activated cell sorter Aria II into 96-well PCR plates (BioRad) containing 20 μL/well of lysis buffer [5 μL of 5X first strand cDNA buffer (Invitrogen), 0.25 μL RNaseOUT (Invitrogen), 1.25 μL dithiothreitol (Invitrogen), 0.625 μL NP-40 (New England Biolabs), and 12.6 μL dH2O]. Plates were immediately frozen on dry ice before storage at −80° C.

Amplification and Cloning of Antibody Variable Sequences

Single B cell PCR and cloning were performed as described previously (Gilman et al., 2016). Briefly, antibody variable genes were amplified by RT-PCR and PCR reactions using cocktails of IgG − and IgA − specific primers and then cloned into S. cerevisiae using the lithium acetate method for chemical transformation (Gietz and Schiestl, 2007). Transformation reactions contained 20 μL of unpurified heavy chain and light chain PCR product and 200 ng of digested heavy and light chain plasmids. After transformation, yeast cells were plated and individual yeast colonies were picked for sequencing and characterization.

Production of Full-Length Human Antibodies

Anti-RSV F IgGs were expressed in S. cerevisiae as described previously (Gilman et al., 2016). Briefly, S. cerevisiae cultures were grown in 24-well plates, and after six days of growth the yeast culture supernatants were harvested by centrifugation and purified over protein A.

High-Throughput Antibody Affinity Measurements

IgG binding affinities for preF and postF were determined by BLI measurements as described previously (Gilman et al., 2016).

Antibody Competition Experiments

Antibody competition assays were performed as previously described (Gilman et al., 2016). The degree of competition was analyzed by measuring the fold reduction in antigen binding in the presence of competitor Fab relative to an antigen-only control. Antibodies that showed a greater than five-fold reduction in binding in the presence of competitor Fab were considered competitors.

Polyreactivity Assay

Antibody polyreactivity was performed essentially as described previously (Jain et al., 2017). Yeast-expressed IgGs were incubated with biotinylated CHO cell membrane preparations and incubated on ice for 20 minutes. Cells were then washed and re-suspended in secondary antibody mix (Extravidin-R-PE, anti-human LC-FITC, and propidium iodide). The mixture was incubated on ice for 20 minutes and then washed twice with PBSF. Cells were then re-suspended in PBSF and run on a FACSCanto II (BD Biosciences). The mean fluorescence intensities of binding were normalized using control antibodies that display high, medium, or low polyreactivity to assess non-specific binding.

High-Throughput Fluorescence Plate Reader Neutralization Assay

A total of 2.4×10 4 HEp-2 cells/well in 30 μL culture medium were seeded in 384-well black optical-bottom plates (Nunc®384-well plates, Thermo Scientific). Antibodies were diluted four-fold starting at 100 μg/mL. An equal volume of recombinant mKate-RSV A2 or mKate-RSV B 18537 was then added and incubated at 37° C. for 1 hour. After incubation, 50 μl of the antibody-virus mixture was added to the HEp-2 cells and incubated at 37° C. for 22-24 hours. After incubation, the fluorescence intensity of each well was measured using a microplate reader at an excitation of 588 nm and an emission of 635 nm (SpectraMax Paradigm). Neutralization IC 50 s were calculated using GraphPad Prism (GraphPad Software Inc.).

Production of ADI-14359, ADI-19425, and AM22 Fabs and Variants

Plasmids encoding the heavy and light chains of ADI-14359, ADI-19425 or AM22 were co-transfected at a 1:1 ratio into Expi293F cells. Point mutants were generated using MegaPrimer PCR and were expressed in FreeStyle 293-F cells. Fabs were purified using CaptureSelect IgG-CH1 affinity matrix (Life Technologies) and were further purified by size-exclusion chromatography on a Superdex 200 column (GE Healthcare).

Production of Protein Complexes for Crystallization

A mammalian expression vector encoding RSV F ΔFP (postF) with a C-terminal HRV 3C cleavage site, 8X HisTag and StrepTagII was transfected into FreeStyle 293-F cells and 5 μM kifunensine was added approximately 4 hours after transfection. The secreted protein was purified using Strep-Tactin resin (IBA), then treated with 10% (wt/wt) EndoH to remove N-linked glycans, followed by 10 U/mg of HRV 3C to remove tags. The protein was then purified by size-exclusion chromatography using a Superdex 200 column (GE) in buffer containing 2 mM Tris pH 8, 200 mM NaCl and 0.02% NaN 3 .

To produce the ADI-14359 Fab-postF complex, purified F ΔFP was combined with a 1.5-fold molar excess of ADI-14359 Fab and incubated at room temperature for approximately 30 minutes. Excess Fab was separated from the complex by size-exclusion chromatography using a Superose 6 column (GE Healthcare Biosciences) in buffer containing 2 mM Tris pH 8, 200 mM NaCl and 0.02% NaN 3 . The complex eluted with a retention volume indicative of a complex with 1-2 Fabs bound per postF trimer, suggesting that ADI-14359 Fab may bind sub-stoichiometrically to postF.

To produce the ADI-19425-AM22-preF ternary complex, purified PR-DM was combined with a 1.5-fold molar excess of both ADI-19425 Fab and AM22 Fab. Binding took place at room temperature for roughly 30 minutes before the ternary complex and excess Fab were separated by size-exclusion chromatography using a Superdex 200 column (GE Healthcare) in 2 mM Tris pH 8, 200 mM NaCl and 0.02% NaN 3 .

Crystallization and Data Collection

The ADI-14359 Fab-postF complex was crystallized by the hanging-drop vapor-diffusion method by mixing 1.33 μL of protein at a concentration of 4.45 mg/mL with 0.67 μL of reservoir solution composed of 13% polyethylene glycol (PEG) 8000 and 0.43 M ammonium citrate pH 8.5. Cryo-preservation was performed by hanging the looped crystal over a 1 M sodium chloride solution for approximately 2 minutes prior to plunge freezing in liquid nitrogen. Data were collected to 3.0 Å resolution at SSRL (Stanford Synchrotron Radiation Lightsource, National Accelerator Laboratory)

The unbound ADI-19425 Fab was initially crystallized using the sitting-drop vapor-diffusion method using 50 nL protein at 8.78 mg/ml and 100 nL reservoir solution containing 2.0 M ammonium sulfate and 0.1 M HEPES pH 7.5. These crystals were used to generate a seek solution and the final crystals were obtained using 50 nL protein at 8.78 mg/ml, 50 nL seed solution and 100 nL reservoir solution containing 1.5 M ammonium sulfate, 0.1 M sodium chloride, and 0.1 M Bis-Tris pH 6.5. Crystals were soaked in a solution of reservoir containing a final concentration of 2.5 M ammonium sulfate before being frozen in liquid nitrogen. Data were collected to 1.7 Å resolution at the SBC beamline 19-ID (Advanced Photon Source, Argonne National Laboratory).

The ADI-19425-AM22-preF ternary complex was crystallized by the sitting-drop vapor-diffusion method using 100 nL of protein solution at a concentration of 4.80 mg/mL and 100 nL of reservoir solution containing 0.1 M sodium citrate pH 5.5, 10% isopropanol and 10% PEG4000. Crystals were soaked in a cryoprotectant solution containing reservoir solution plus 15% 2R,3R-butanediol before being frozen in liquid nitrogen. Data were collected to 4.3 Å at the SBC beamline 19-ID (Advanced Photon Source, Argonne National Laboratory).

Structure Determination, Model Building and Refinement

Diffraction data were indexed and integrated using iMOSFLM (Battye et al., 2011) and merged and scaled with AIMLESS (Evans and Murshudov, 2013). Molecular replacement solutions were obtained with PHASER (McCoy et al., 2007) and the structures were refined using PHENIX (Adams et al., 2002) and built manually using Coot (Emsley and Cowtan, 2004). Software used for processing and visualization of X-ray diffraction data was curated by SBGrid and accessed using the CCP4i interface (Collaborative Computational Project, 1994; Morin et al., 2013; Potterton et al., 2003). Data collection and refinement statistics for the three crystal structures are presented in Table 2.

The ADI-14359-postF complex formed crystals in space group P2 1 2 1 2 1 and a molecular replacement solution was found using the previously solved postF structure (PDB ID: 3RRT), the heavy chain from 2D1 Fab (PDB ID: 3QHZ), and the light-chain from 5-51/O12 Fab (PDB ID: 4KMT) as search models. The asymmetric unit contained one postF trimer with only one ADI-14359 Fab bound per trimer. The model was built manually in Coot and refined in PHENIX using non-crystallographic symmetry (NCS) and reference model restraints to an Rwork/Rfree of 22.0/25.3%.

The unbound ADI-19425 Fab also formed crystals in P212121, and the heavy chain from MJ5 Fab (PDB ID: 3EYQ) and the light chain from LDLR competitive Fab (PDB ID: 3H42) were used as search models in molecular replacement. The structure was manually built in Coot and refined in PHENIX to an Rwork/Rfree of 17.4/20.4%. The ADI-19425-AM22-preF complex formed crystals in space group P41212 and a molecular replacement solution was found using the refined structures of the unbound ADI-19425 Fab and the complex of preF bound to AM22 Fab as search ensembles. The asymmetric unit contained a single preF trimer bound by three molecules of AM22 Fab and three molecules of 19425 Fab. The model was built manually in Coot and refined in PHENIX using non-crystallographic symmetry (NCS) and reference model restraints to an Rwork/Rfree of 22.2/25.5%.

Fab Affinity Measurements for ADI-14359, ADI-19425, and Variants

The affinity of ADI-14359 Fab for postF was measured using surface plasmon resonance (SPR). Purified postF (RSV F ΔFP) with a C-terminal HRV 3C cleavage site, 8X HisTag and StrepTagII was captured on the sample flow cell of an NTA sensor chip to approximately 115 RU per cycle using a Biacore X100 (GE Healthcare). The NTA chip was regenerated between each cycle with

0.35 M EDTA followed by 0.5 mM NiCl 2 . A buffer-only reference sample (HBS-P+pH 8) was injected over both flow cells, followed by a 2-fold serial dilution of ADI-14359 Fab from 800 nM to 6.25 nM, starting with the lowest concentration, and a duplication of the 100 nM sample. The data were double-reference subtracted, then fit to a 1:1 binding model using Scrubber. Binding of ADI-14359 Fab to the postF K390A variant was measured in a similar manner, with capture of approximately 100 RU per cycle and injection of a buffer-only reference, followed by a 2-fold serial dilution of Fab from 1.6 μM to 6.25 nM, with a duplication of the 100 nM concentration. The data were double-reference subtracted, but the total response was too low to allow an affinity to be calculated. For the germline variant of ADI-14359 (R50L), approximately 115 RU of postF was captured on the NTA chip before injection of a buffer-only reference, followed by a 2-fold serial dilution of ADI-14359 R50L Fab from 20 μM to 78 nM. The data were double reference subtracted and fit using a steady-state affinity model in Scrubber.

Similar SPR experiments were performed to measure the binding between ADI-19425 Fab and preF. Purified preF (DS-Cav1) with a C-terminal 8X HisTag and AviTag was captured on the sample flow cell of an NTA sensor chip to approximately 150 RU. A buffer-only reference sample (HBS-P+pH 8.0) was injected over both the sample and reference flow cells, followed by a 2-fold serial dilution of ADI-19425 Fab from 40 nM to 1.25 nM, with a duplication of the 10 nM concentration. For the ADI-19425 Fab variants (heavy chain Y56A, light chain Y31A, and light chain Y91A), roughly 150 RU of preF was captured on the NTA chip before the injection of a buffer-only reference, followed by a 2-fold serial dilution of ADI-19425 Fab variant from 1000 nM to 31.25 nM, with a duplication of the 250 nM concentration. The data were double reference subtracted and fit using a 1:1 binding model in Scrubber.

Data Resources

Antibody sequences will be deposited in GenBank. Atomic coordinates and structure factors for the 14359-postF complex structure, the unbound 19425 Fab, and the 19425-AM22-preF complex structure have been deposited with the Protein Data Bank under accession codes 6APB, 6APC, and 6APD.

REFERENCES

All references cited herein including, without limitation, patents, patent applications, and non-patent references and publications referenced throughout, are hereby expressly incorporated by reference in their entireties for all purposes.

• Acosta, P. L., Caballero, M. T., and Polack, F. P. (2015). Brief History and Characterization of Enhanced Respiratory Syncytial Virus Disease. Clin Vaccine Immunol 23, 189-195. • Adams, P. D., Grosse-Kunstleve, R. W., Hung, L. W., Ioerger, T. R., McCoy, A. J., Moriarty, N. W., Read, R. J., Sacchettini, J. C., Sauter, N. K., and Terwilliger, T. C. (2002). PHENIX: building new software for automated crystallographic structure determination. Acta Crystallogr D Biol Crystallogr 58, 1948-1954. • Anderson, L. J., Dormitzer, P. R., Nokes, D. J., Rappuoli, R., Roca, A., and Graham, B. S. (2013). Strategic priorities for respiratory syncytial virus (RSV) vaccine development. Vaccine 31 Suppl 2, B209-215. • Anderson, L. J., Hierholzer, J. C., Stone, Y. O., Tsou, C., and Fernie, B. F. (1986). Identification of epitopes on respiratory syncytial virus proteins by competitive binding immunoassay. J Clin Microbiol 23, 475-480. • Bailey, J. R., Flyak, A. I., Cohen, V. J., Li, H., Wasilewski, L. N., Snider, A. E., Wang, S., Learn, G. H., Kose, N., Loerinc, L., et al. (2017). Broadly neutralizing antibodies with few somatic mutations and hepatitis C virus clearance. JCI Insight 2. • Battles, M. B., Langedijk, J. P., Furmanova-Hollenstein, P., Chaiwatpongsakorn, S., Costello, H. M., Kwanten, L., Vranckx, L., Vink, P., Jaensch, S., Jonckers, T. H., et al. (2016). Molecular mechanism of respiratory syncytial virus fusion inhibitors. Nat Chem Biol 12, 87-93. • Battye, T. G., Kontogiannis, L., Johnson, O., Powell, H. R., and Leslie, A. G. (2011). iMOSFLM: a new graphical interface for diffraction-image processing with MOSFLM. Acta Crystallogr D Biol Crystallogr 67, 271-281. • Beeler, J. A., and van Wyke Coelingh, K. (1989). Neutralization epitopes of the F glycoprotein of respiratory syncytial virus: effect of mutation upon fusion function. J Virol 63, 2941-2950. • Bornholdt, Z. A., Turner, H. L., Murin, C. D., Li, W., Sok, D., Souders, C. A., Piper, A. E., Goff, A., Shamblin, J. D., Wollen, S. E., et al. (2016). Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak. Science 351, 1078-1083. • Chin, J., Magoffin, R. L., Shearer, L. A., Schieble, J. H., and Lennette, E. H. (1969). Field evaluation of a respiratory syncytial virus vaccine and a trivalent parainfluenza virus vaccine in a pediatric population. Am J Epidemiol 89, 449-463. • Collaborative Computational Project, N. (1994). The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr 50, 760-763. • Corti, D., Bianchi, S., Vanzetta, F., Minola, A., Perez, L., Agatic, G., Guarino, B., Silacci, C., Marcandalli, J., Marsland, B. J., et al. (2013). Cross-neutralization of four paramyxoviruses by a human monoclonal antibody. Nature 501, 439-443. • Crooks, G. E., Hon, G., Chandonia, J. M., and Brenner, S. E. (2004). WebLogo: a sequence logo generator. Genome Res 14, 1188-1190. • DeKosky, B. J., Ippolito, G. C., Deschner, R. P., Lavinder, J. J., Wine, Y., Rawlings, B. M., Varadarajan, N., Giesecke, C., Dorner, T., Andrews, S. F., et al. (2013). High-throughput sequencing of the paired human immunoglobulin heavy and light chain repertoire. Nat Biotechnol 31, 166-169. • Doria-Rose, N. A., Klein, R. M., Daniels, M. G., O'Dell, S., Nason, M., Lapedes, A., Bhattacharya, T., Migueles, S. A., Wyatt, R. T., Korber, B. T., et al. (2010). Breadth of human immunodeficiency virus-specific neutralizing activity in sera: clustering analysis and association with clinical variables. J Virol 84, 1631-1636. • Ekiert, D. C., Bhabha, G., Elsliger, M. A., Friesen, R. H., Jongeneelen, M., Throsby, M., Goudsmit, J., and Wilson, I. A. (2009). Antibody recognition of a highly conserved influenza virus epitope. Science 324, 246-251. • Emsley, P., and Cowtan, K. (2004). Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60, 2126-2132. • Esposito, S., Scarselli, E., Lelii, M., Scala, A., Vitelli, A., Capone, S., Fornili, M., Biganzoli, E., Orenti, A., Nicosia, A., et al. (2016). Antibody response to respiratory syncytial virus infection in children <18 months old. Hum Vaccin Immunother 12, 1700-1706. • Evans, P. R., and Murshudov, G. N. (2013). How good are my data and whatis the resolution? Acta Crystallogr D Biol Crystallogr 69, 1204-1214. • Fuentes, S., Coyle, E. M., Beeler, J., Golding, H., and Khurana, S. (2016). Antigenic Fingerprinting following Primary RSV Infection in Young Children Identifies Novel Antigenic Sites and Reveals Unlinked Evolution of Human Antibody Repertoires to Fusion and Attachment Glycoproteins. PLoS Pathog 12, e1005554. • Fulginiti, V. A., Eller, J. J., Sieber, O. F., Joyner, J. W., Minamitani, M., and Meiklejohn, G. (1969). Respiratory virus immunization. I. A field trial of two inactivated respiratory virus vaccines; an aqueous trivalent parainfluenza virus vaccine and an alum-precipitated respiratory syncytial virus vaccine. Am J Epidemiol 89, 435-448. • Gans, H., Yasukawa, L., Rinki, M., DeHovitz, R., Forghani, B., Beeler, J., Audet, S., Maldonado, Y., and Arvin, A. M. (2001). Immune responses to measles and mumps vaccination of infants at 6, 9, and 12 months. J Infect Dis 184, 817-826. • Garcia-Barreno, B., Palomo, C., Penas, C., Delgado, T., Perez-Brena, P., and Melero, J. A. (1989). Marked differences in the antigenic structure of human respiratory syncytial virus F and G glycoproteins. J Virol 63, 925-932. • Gietz, R. D., and Schiestl, R. H. (2007). High-efficiency yeast transformation using the LiAc/SS carrier DNA/PEG method. Nat Protoc 2, 31-34. • Gilman, M. S., Castellanos, C. A., Chen, M., Ngwuta, J. O., Goodwin, E., Moin, S. M., Mas, V., Melero, J. A., Wright, P. F., Graham, B. S., et al. (2016). Rapid profiling of RSV antibody repertoires from the memory B cells of naturally infected adult donors. Sci Immunol 1. • Gilman, M. S., Moin, S. M., Mas, V., Chen, M., Patel, N. K., Kramer, K., Zhu, Q., Kabeche, S. C., Kumar, A., Palomo, C., et al. (2015). Characterization of a Prefusion-Specific Antibody That Recognizes a Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoprotein. PLoS Pathog 11, e1005035. • Glezen, W. P., Taber, L. H., Frank, A. L., and Kasel, J. A. (1986). Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child 140, 543-546. • Graham, B. S. (2017). Vaccine development for respiratory syncytial virus. Curr Opin Virol 23, 107-112. • Gray, E. S., Madiga, M. C., Hermanus, T., Moore, P. L., Wibmer, C. K., Tumba, N. L., Werner, L., Mlisana, K., Sibeko, S., Williamson, C., et al. (2011). The neutralization breadth of HIV-1 develops incrementally over four years and is associated with CD4+ T cell decline and high viral load during acute infection. J Virol 85, 4828-4840. • Griffin, M. P., Khan, A. A., Esser, M. T., Jensen, K., Takas, T., Kankam, M. K., Villafana, T., and Dubovsky, F. (2017). Safety, Tolerability, and Pharmacokinetics of MEDI8897, the Respiratory Syncytial Virus Prefusion F-Targeting Monoclonal Antibody with an Extended Half-Life, in Healthy Adults. Antimicrob Agents Chemother 61. • Group, T. I.-R. S. (1998). Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics 102, 531-537. • Hall, C. B., Walsh, E. E., Long, C. E., and Schnabel, K. C. (1991). Immunity to and frequency of reinfection with respiratory syncytial virus. J Infect Dis 163, 693-698. • Henderson, F. W., Collier, A. M., Clyde, W. A., Jr., and Denny, F. W. (1979). Respiratory-syncytial-virus infections, reinfections and immunity. A prospective, longitudinal study in young children. N Engl J Med 300, 530-534. • Homaira, N., Rawlinson, W., Snelling, T. L., and Jaffe, A. (2014). Effectiveness of Palivizumab in Preventing RSV Hospitalization in High Risk Children: A Real-World Perspective. Int J Pediatr 2014, 571609. • Huang, K., Incognito, L., Cheng, X., Ulbrandt, N.D., and Wu, H. (2010). Respiratory syncytial virus-neutralizing monoclonal antibodies motavizumab and palivizumab inhibit fusion. J Virol 84, 8132-8140. • IJspeert, H., van Schouwenburg, P. A., van Zessen, D., Pico-Knijnenburg, I., Driessen, G. J., Stubbs, A. P., and van der Burg, M. (2016). Evaluation of the Antigen-Experienced B-Cell Receptor Repertoire in Healthy Children and Adults. Front Immunol 7, 410. • Jain, T., Sun, T., Durand, S., Hall, A., Houston, N. R., Nett, J. H., Sharkey, B., Bobrowicz, B., Caffry, I., Yu, Y., et al. (2017). Biophysical properties of the clinical-stage antibody landscape. Proc Natl Acad Sci USA 114, 944-949. • Jans, J., Pettengill, M., Kim, D., van der Made, C., de Groot, R., Henriet, S., de Jonge, M. I., Ferwerda, G., and Levy, 0. (2016). Human newborn B cells mount an interferon-alpha/beta receptor-dependent humoral response to respiratory syncytial virus. J Allergy Clin Immunol. • Jardine, J. G., Kulp, D. W., Havenar-Daughton, C., Sarkar, A., Briney, B., Sok, D., Sesterhenn, F., Ereno-Orbea, J., Kalyuzhniy, O., Deresa, I., et al. (2016). HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen. Science 351, 1458-1463. • Kamal-Bahl, S., Doshi, J., and Campbell, J. (2002). Economic analyses of respiratory syncytial virus immunoprophylaxis in high-risk infants: a systematic review. Arch Pediatr Adolesc Med 156, 1034-1041. • Kapikian, A. Z., Mitchell, R. H., Chanock, R. M., Shvedoff, R. A., and Stewart, C. E. (1969). An epidemiologic study of altered clinical reactivity to respiratory syncytial (RS) virus infection in children previously vaccinated with an inactivated RS virus vaccine. Am J Epidemiol 89, 405-421. • Kashyap, A. K., Steel, J., Oner, A. F., Dillon, M. A., Swale, R. E., Wall, K. M., Perry, K. J., Faynboym, A., Ilhan, M., Horowitz, M., et al. (2008). Combinatorial antibody libraries from survivors of the Turkish H5N1 avian influenza outbreak reveal virus neutralization strategies. Proc Natl Acad Sci USA 105, 5986-5991. • Kelly, R. L., Sun, T., Jain, T., Caffry, I., Yu, Y., Cao, Y., Lynaugh, H., Brown, M., Vasquez, M., Wittrup, K. D., et al. (2015). High throughput cross-interaction measures for human IgG1 antibodies correlate with clearance rates in mice. MAbs, 0. • Killikelly, A. M., Kanekiyo, M., and Graham, B. S. (2016). Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus. Sci Rep 6, 34108. • Kim, H. W., Canchola, J. G., Brandt, C. D., Pyles, G., Chanock, R. M., Jensen, K., and Parrott, R. H. (1969). Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am J Epidemiol 89, 422-434. • Krarup, A., Truan, D., Furmanova-Hollenstein, P., Bogaert, L., Bouchier, P., Bisschop, I. J., Widjojoatmodjo, M. N., Zahn, R., Schuitemaker, H., McLellan, J. S., et al. (2015). A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism. Nat Commun 6, 8143. • Kristjansson, S., Bjarnarson, S. P., Wennergren, G., Palsdottir, A. H., Arnadottir, T., Haraldsson, A., and Jonsdottir, I. (2005). Respiratory syncytial virus and other respiratory viruses during the first 3 months of life promote a local TH2-like response. J Allergy Clin Immunol 116, 805-811. • Lambert, D. M., Barney, S., Lambert, A. L., Guthrie, K., Medinas, R., Davis, D. E., Bucy, T., Erickson, J., Merutka, G., and Petteway, S. R., Jr. (1996). Peptides from conserved regions of paramyxovirus fusion (F) proteins are potent inhibitors of viral fusion. Proc Natl Acad Sci USA 93, 2186-2191. • Lambert, L., Sagfors, A. M., Openshaw, P. J., and Culley, F. J. (2014). Immunity to RSV in Early-Life. Front Immunol 5, 466. • Legg, J. P., Hussain, I. R., Warner, J. A., Johnston, S. L., and Warner, J. O. (2003). Type 1 and type 2 cytokine imbalance in acute respiratory syncytial virus bronchiolitis. Am J Respir Crit Care Med 168, 633-639. • Lerner, R. A. (2011). Rare antibodies from combinatorial libraries suggests an S.O.S. component of the human immunological repertoire. Mol Biosyst 7, 1004-1012. • Magro, M., Mas, V., Chappell, K., Vazquez, M., Cano, O., Luque, D., Terron, M. C., Melero, J. A., and Palomo, C. (2012). Neutralizing antibodies against the preactive form of respiratory syncytial virus fusion protein offer unique possibilities for clinical intervention. Proc Natl Acad Sci U S A 109, 3089-3094. • McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., and Read, R. J. (2007). Phaser crystallographic software. J Appl Crystallogr 40, 658-674. • McLellan, J. S., Chen, M., Chang, J. S., Yang, Y., Kim, A., Graham, B. S., and Kwong, P. D. (2010a). Structure of a major antigenic site on the respiratory syncytial virus fusion glycoprotein in complex with neutralizing antibody 101F. J Virol 84, 12236-12244. • McLellan, J. S., Chen, M., Kim, A., Yang, Y., Graham, B. S., and Kwong, P. D. (2010b). • Structural basis of respiratory syncytial virus neutralization by motavizumab. Nat Struct Mol Biol 17, 248-250. • McLellan, J. S., Chen, M., Leung, S., Graepel, K. W., Du, X., Yang, Y., Zhou, T., Baxa, U., Yasuda, E., Beaumont, T., et al. (2013). Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody. Science 340, 1113-1117. • McLellan, J. S., Yang, Y., Graham, B. S., and Kwong, P. D. (2011). Structure of respiratory syncytial virus fusion glycoprotein in the postfusion conformation reveals preservation of neutralizing epitopes. J Virol 85, 7788-7796. • Morin, A., Eisenbraun, B., Key, J., Sanschagrin, P. C., Timony, M. A., Ottaviano, M., and Sliz, P. (2013). Collaboration gets the most out of software. Elife 2, e01465. • Mousa, J. J., Kose, N., Matta, P., Gilchuk, P., and Crowe, J. E., Jr. (2017). A novel pre-fusion conformation-specific neutralizing epitope on the respiratory syncytial virus fusion protein. Nat Microbiol 2, 16271. • Murphy, B. R., Alling, D. W., Snyder, M. H., Walsh, E. E., Prince, G. A., Chanock, R. M., Hemming, V. G., Rodriguez, W. J., Kim, H. W., Graham, B. S., et al. (1986). Effect of age and preexisting antibody on serum antibody response of infants and children to the F and G glycoproteins during respiratory syncytial virus infection. J Clin Microbiol 24, 894-898. • Murphy, B. R., and Walsh, E. E. (1988). Formalin-inactivated respiratory syncytial virus vaccine induces antibodies to the fusion glycoprotein that are deficient in fusion-inhibiting activity. J Clin Microbiol 26, 1595-1597. • Ngwuta, J. O., Chen, M., Modjarrad, K., Joyce, M. G., Kanekiyo, M., Kumar, A., Yassine, H. M., Moin, S. M., Killikelly, A. M., Chuang, G. Y., et al. (2015). Prefusion F-specific antibodies determine the magnitude of RSV neutralizing activity in human sera. Sci Transl Med 7, 309ra162. • Panda, S., and Ding, J. L. (2015). Natural antibodies bridge innate and adaptive immunity. J Immunol 194, 13-20. • PATH (2017). RSV Vaccine and mAb Snapshot. • Polack, F. P., Teng, M. N., Collins, P. L., Prince, G. A., Exner, M., Regele, H., Lirman, D. D., Rabold, R., Hoffman, S. J., Karp, C. L., et al. (2002). A role for immune complexes in enhanced respiratory syncytial virus disease. J Exp Med 196, 859-865. • Potterton, E., Briggs, P., Turkenburg, M., and Dodson, E. (2003). A graphical user interface to the CCP4 program suite. Acta Crystallogr D Biol Crystallogr 59, 1131-1137. • Rechavi, E., Lev, A., Lee, Y. N., Simon, A. J., Yinon, Y., Lipitz, S., Amariglio, N., Weisz, B., Notarangelo, L. D., and Somech, R. (2015). Timely and spatially regulated maturation of B and T cell repertoire during human fetal development. Sci Transl Med 7, 276ra225. • Reed, J. H., Jackson, J., Christ, D., and Goodnow, C. C. (2016). Clonal redemption of autoantibodies by somatic hypermutation away from self-reactivity during human immunization. J Exp Med 213, 1255-1265. • Reichert, J. M. (2016). Antibodies to watch in 2016. MAbs 8, 197-204. • Ridings, J., Dinan, L., Williams, R., Roberton, D., and Zola, H. (1998). Somatic mutation of immunoglobulin V(H)6 genes in human infants. Clin Exp Immunol 114, 33-39. • Rossey, I., Gilman, M. S., Kabeche, S. C., Sedeyn, K., Wrapp, D., Kanekiyo, M., Chen, M., Mas, V., Spitaels, J., Melero, J. A., et al. (2017). Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state. Nat Commun 8, 14158. • Sande, C. J., Cane, P. A., and Nokes, D. J. (2014). The association between age and the development of respiratory syncytial virus neutralising antibody responses following natural infection in infants. Vaccine 32, 4726-4729. • Saravia, J., You, D., Shrestha, B., Jaligama, S., Siefker, D., Lee, G. I., Harding, J. N., Jones, T. L., Rovnaghi, C., Bagga, B., et al. (2015). Respiratory Syncytial Virus Disease Is Mediated by Age-Variable IL-33. PLoS Pathog 11, e1005217. • Sastre, P., Melero, J. A., Garcia-Barreno, B., and Palomo, C. (2005). Comparison of affinity chromatography and adsorption to vaccinia virus recombinant infected cells for depletion of antibodies directed against respiratory syncytial virus glycoproteins present in a human immunoglobulin preparation. J Med Virol 76, 248-255. • Sather, D. N., Armann, J., Ching, L. K., Mavrantoni, A., Sellhorn, G., Caldwell, Z., Yu, X., Wood, B., Self, S., Kalams, S., et al. (2009). Factors associated with the development of cross-reactive neutralizing antibodies during human immunodeficiency virus type 1 infection. J Virol 83, 757-769. • Shi, T., McAllister, D. A., O'Brien, K. L., Simoes, E. A. F., Madhi, S. A., Gessner, B. D., Polack, F. P., Balsells, E., Acacio, S., Aguayo, C., et al. (2017). Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet. • Shinoff, J. J., O'Brien, K. L., Thumar, B., Shaw, J. B., Reid, R., Hua, W., Santosham, M., and Karron, R. A. (2008). Young infants can develop protective levels of neutralizing antibody after infection with respiratory syncytial virus. J Infect Dis 198, 1007-1015. • Siegrist, C. A., and Aspinall, R. (2009). B-cell responses to vaccination at the extremes of age. Nat Rev Immunol 9, 185-194. • Simek, M. D., Rida, W., Priddy, F. H., Pung, P., Carrow, E., Laufer, D. S., Lehrman, J. K., Boaz, M., Tarragona-Fiol, T., Miiro, G., et al. (2009). Human immunodeficiency virus type 1 elite neutralizers: individuals with broad and potent neutralizing activity identified by using a high-throughput neutralization assay together with an analytical selection algorithm. J Virol 83, 7337-7348. • Sok, D., Briney, B., Jardine, J. G., Kulp, D. W., Menis, S., Pauthner, M., Wood, A., Lee, E. C., Le, K. M., Jones, M., et al. (2016). Priming HIV-1 broadly neutralizing antibody precursors in human Ig loci transgenic mice. Science 353, 1557-1560. • Sui , J., Hwang, W. C., Perez, S., Wei, G., Aird, D., Chen, L. M., Santelli, E., Stec, B., Cadwell, G., Ali, M., et al. (2009). Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol 16, 265-273. • Swanson, K. A., Settembre, E. C., Shaw, C. A., Dey, A. K., Rappuoli, R., Mandl, C. W., Dormitzer, P. R., and Carfi, A. (2011). Structural basis for immunization with postfusion respiratory syncytial virus fusion F glycoprotein (RSV F) to elicit high neutralizing antibody titers. Proc Natl Acad Sci USA 108, 9619-9624. • Swers, J. S., Kellogg, B. A., and Wittrup, K. D. (2004). Shuffled antibody libraries created by in vivo homologous recombination and yeast surface display. Nucleic Acids Res 32, e36. • Thomson, C. A., Bryson, S., McLean, G. R., Creagh, A. L., Pai, E. F., and Schrader, J. W. (2008). Germline V-genes sculpt the binding site of a family of antibodies neutralizing human cytomegalovirus. EMBO J 27, 2592-2602. • Throsby, M., van den Brink, E., Jongeneelen, M., Poon, L. L., Alard, P., Cornelissen, L., Bakker, A., Cox, F., van Deventer, E., Guan, Y., et al. (2008). Heterosubtypic neutralizing monoclonal antibodies cross-protective against H5N1 and H1N1 recovered from human IgM+ memory B cells. PLoS One 3, e3942. • Tiller, T., Meffre, E., Yurasov, S., Tsuiji, M., Nussenzweig, M. C., and Wardemann, H. (2008). Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. J Immunol Methods 329, 112-124. • Trang, N. V., Braeckman, T., Lernout, T., Hau, V. T., Anh le, T. K., Luan le, T., Van Damme, P., and Anh, D. D. (2014). Prevalence of rotavirus antibodies in breast milk and inhibitory effects to rotavirus vaccines. Hum Vaccin Immunother 10, 3681-3687. • Troisi, C. L., Hollinger, F. B., Krause, D. S., and Pickering, L. K. (1997). Immunization of seronegative infants with hepatitis A vaccine (HAVRIX; SKB): a comparative study of two dosing schedules. Vaccine 15, 1613-1617. • Wang, J., He, Y., Jin, D., Liu, J., Zheng, J., Yuan, N., Bai, Y., Yan, T., Yang, Y., Liu, Y., et al. (2017). No response to hepatitis B vaccine in infants born to HBsAg(+) mothers is associated to the transplacental transfer of HBsAg. Infect Dis (Lond), 1-8. • Wen, X., Mousa, J. J., Bates, J. T., Lamb, R. A., Crowe, J. E., Jr., and Jardetzky, T. S. (2017). Structural basis for antibody cross-neutralization of respiratory syncytial virus and human metapneumovirus. Nat Microbiol 2, 16272. • Williams, J. V., Weitkamp, J. H., Blum, D. L., LaFleur, B. J., and Crowe, J. E., Jr. (2009). The human neonatal B cell response to respiratory syncytial virus uses a biased antibody variable gene repertoire that lacks somatic mutations. Mol Immunol 47, 407-414. • Wu, S. J., Schmidt, A., Beil, E. J., Day, N.D., Branigan, P. J., Liu, C., Gutshall, L. L., Palomo, C., Furze, J., Taylor, G., et al. (2007). Characterization of the epitope for anti-human respiratory syncytial virus F protein monoclonal antibody 101F using synthetic peptides and genetic approaches. J Gen Virol 88, 2719-2723. • Xu, Y., Roach, W., Sun, T., Jain, T., Prinz, B., Yu, T. Y., Torrey, J., Thomas, J., Bobrowicz, P., Vasquez, M., et al. (2013). Addressing polyspecificity of antibodies selected from an in vitro yeast presentation system: a FACS-based, high-throughput selection and analytical tool. Protein Eng Des Sel 26, 663-670. • Yacoob, C., Pancera, M., Vigdorovich, V., Oliver, B. G., Glenn, J. A., Feng, J., Sather, D. N., McGuire, A. T., and Stamatatos, L. (2016). Differences in Allelic Frequency and CDRH3 Region Limit the Engagement of HIV Env Immunogens by Putative VRC01 Neutralizing Antibody Precursors. Cell Rep 17, 1560-1570. • Yeung, Y. A., Foletti, D., Deng, X., Abdiche, Y., Strop, P., Glanville, J., Pitts, S., Lindquist, K., Sundar, P. D., Sirota, M., et al. (2016). Germline-encoded neutralization of a Staphylococcus aureus virulence factor by the human antibody repertoire. Nat Commun 7, 13376. • Zhang, X., Zhivaki, D., and Lo-Man, R. (2017). Unique aspects of the perinatal immune system. Nat Rev Immunol. • Zhu, Q., McLellan, J. S., Kallewaard, N. L., Ulbrandt, N.D., Palaszynski, S., Zhang, J., Moldt, B., Khan, A., Svabek, C., McAuliffe, J. M., et al. (2017). A highly potent extended half-life antibody as a potential RSV vaccine surrogate for all infants. Sci Transl Med 9

Example 2. Isolation and Characterization of Anti-RSV F-Specific Human Infant Antibodies from Adenoid and PBMCs

Applicant has comprehensively profiled the human infant antibody response to RSV F by isolating and characterizing over 800 RSV F-specific monoclonal antibodies from paired nasopharyngeal adenoid (adenoid) and peripheral blood samples (PBMCs) of RSV-infected infants, and used these antibodies to characterize the infant antibody response as well as develop a framework for the rational design of age-specific RSV vaccines. RSV F-specific memory B cell responses were detected in the adenoids of all 6 children, and the adenoid-derived antibodies showed overall higher binding affinities and neutralization potencies compared to antibodies isolated from paired peripheral blood samples. Approximately 25% of the neutralizing antibodies isolated from adenoid tissue were derived from a unique population of IgM + and/or IgD + memory B cells that contained a high load of somatic mutations but lacked expression of classical memory B cell markers. The collective results provide insight into the mucosal B cell response to RSV and have implications for the development of vaccines that stimulate potent local responses.

Isolation of RSV F-Specific B Cells from Paired Adenoid and Peripheral Blood Samples

To analyze and compare the mucosal and systemic B cell response to natural RSV infection, paired adenoid tissue and peripheral blood samples were obtained from 6 young children between the ages of 2 and 4 years old who were undergoing tonsillectomy (Supplementary Table 1). Adenoids were used as a representative source of respiratory mucosal lymphocytes because this lymphoid tissue has been previously shown to be an important induction site for B cells that migrate to the respiratory tract and associated glands (Czerkinsky et al 1994, McGhee 2000, Brandtzaeg P1. 2011). The adenoid's location at the site of entry into the upper respiratory tract also suggests a role in anti-RSV immunity. Although none of the children had a documented history of RSV infection, previous studies have shown that essentially all children have been infected by RSV at least once by the age of 2. Consistent with the notion of prior RSV exposure, serum samples obtained from all six children displayed neutralizing activity against RSV-A2 (Supplementary Table 1).

SUPPLEMENTARY TABLE 1

Neutralizing activity against RSV-A2

50% RSV neutralization titer

Age Adenoid Adenoid

Subject Gender (yrs) Plasma filter supernatant

2635 M 3.60 545 9 9

2637 F 3.13 639 <4 13

2665 M 2.82 506 <4 <4

2666 F 3.05 1702 13 177

2849 M 2.79 5133 4 55

2850 M 2.97 720 6 5

To assess the magnitude of the RSV F-specific B cell response in both anatomical compartments, the adenoid and PBMC samples were stained with a panel of B cell markers (CD19, CD20, IgG, IgA, CD27, and FCRL4) and fluorescently-labeled tetramers of RSV preF and postF and analyzed by flow cytometry ( FIG. 13 A ). RSV F-reactive B cells were detected in the adenoid samples from all 6 donors but in only 4 of the 6 corresponding PBMC samples ( FIG. 13 B ). The frequency of RSV F-specific B cells in the adenoid and PBMC samples ranged from 0.03-0.22% and 0-0.19%, respectively. There was no clear correlation between 1) the frequency of RSV F-reactive B cells in peripheral blood and adenoid tissue, and 2) the frequency of RSV F-reactive B cells in either compartment ( FIG. 14 A ) and serum neutralization titer ( FIG. 14 B ). The latter result is consistent with previous studies showing a lack of correlation between the frequencies of antigen-specific memory B cells and serum titers of antigen specific IgG.

Next, between 100-300 RSV F-reactive B cells from both the adenoid and PBMC samples from each of the four donors that had detectable RSV F-specific B cell responses in both compartments were single-cell sorted. Although all RSV F-reactive B cells were sorted, index sorting allowed for the determination of the B cell surface markers expressed on each sorted cell. This analysis showed that the RSV F-specific B cell subset distribution varied considerably between the two compartments and among the four donors ( FIG. 13 B ). For example, in some donors, there was a higher proportion of RSV F-specific IgG + memory B cells in peripheral blood compared to adenoid tissue (e.g. donor 2635 and donor 2849), whereas the converse was observed in other donors (e.g. donor 2665). Notably, in all four donors, there was little to no enrichment for RSV F-specific IgA + B cells in the adenoid samples relative to the corresponding PBMC samples, and in one donor (donor 2665) there was a substantially higher proportion of RSV F-specific IgA + B cells in peripheral blood compared to adenoid tissue ( FIG. 13 B ). Furthermore, in all donors, a considerable proportion (21-52%) of RSV F-specific B cells in both compartments were not class-switched and lacked the expression of the classical memory B cell marker CD27. Since previous studies have shown that the inhibitory receptor FcRL4 is expressed on a proportion of tissue-resident memory B cells (Ehrhardt et al, J Exp Med 2005), it was analyzed whether this marker was preferentially expressed on certain subsets of adenoid-derived B cells. A proportion of B cell clones within most of the subsets in both compartments expressed FcRL4, with the exception of the IgG − IgA − CD27 − and adenoid-resident IgG + CD27 − subsets, and the large majority of FcRL4 + B cells in both compartments were of the IgA isotype ( FIG. 13 C ). Therefore, it was concluded that natural RSV infection induces memory B cell responses in the adenoids of young children, and the contribution of different memory B cell populations to the RSV-specific response varies among donors and between the mucosal and systemic compartments.

An Atypical Population of RSV-Specific Memory B Cells is Enriched in Adenoid Tissue

To further characterize the RSV-specific mucosal B cell response, the antibody variable heavy (VH) and variable light (VL) chain sequences from the sorted B cells were amplified by single cell-PCR. Over 800 cognate VH-VL pairs were cloned into an IgG1 expression vector for sequencing and IgG production. Sequence analysis revealed that the RSV F-specific antibody repertoires were highly diverse in both compartments in all donors, each containing few to no expanded clonal lineages ( FIG. 15 A ). Although deeper sequencing would be required to accurately determine the degree of overlap between the RSV F-specific clones in each compartment, one clonal lineage was identified in both the adenoid- and PBMC-derived antibody panels isolated from donor 2635 (supplementary table 2), suggesting that at least a proportion of RSV F-specific B cells recirculate between the mucosal and systemic compartments.

SUPPLEMENTARY TABLE 2

Clonal lineage from donor 2635

VL CDR1 VL FR2 VL CDR2

RSSQSLLHSNGFNYLD (SEQ ID NO: WYLQKPGQSPQLLIY LGSNRAS

1895) (SEQ ID NO: 1896) (SEQ ID

NO: 1897)

RSSQSLLHSNGFNYLD (SEQ ID NO: WYLQKPGQSPQLLIY LGSNRAS

1895) (SEQ ID NO: 1896) (SEQ ID

NO: 1895)

VL FR3 VL CDR3 VL FR4

GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTLT FGPGTKVEIK

(SEQ ID NO: 1898) (SEQ ID NO: 1899) (SEQ ID

NO: 1900)

GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTLT FGGGTKVEIK

(SEQ ID NO: 1898) (SEQ ID NO: 1899) (SEQ ID

NO: 1901)

Next, the CDRH3 length distribution, VH germline gene usage, and load of somatic mutations in the antibodies isolated from the two compartments were analyzed ( FIG. 15 B ). The median CDRH3 lengths of the antibodies isolated from PBMCs and adenoids were 15 and 16 amino acids, respectively, which is consistent with previously reported median CDRH3 lengths for anti-viral antibodies (Gilman et al., Sci Immunol. 2016; Bornholdt et al., Science 2016; Collis and Martin, J M B 2003). Although the VH germline gene usage was also comparable between the two compartments, there was an enrichment for VH5-51 and VH1-69 in the adenoid-derived antibodies and an enrichment for VH4-34 and VH3-30 in the PBMC-derived antibodies across all four donor repertoires ( FIG. 15 C ). The level of somatic mutation in the antibodies varied among the 4 donors, with the median number of VH nucleotide substitutions ranging from 8-11 in the adenoid-derived antibodies and 7-9 in the PBMC-derived antibodies ( FIG. 16 A and FIG. 17 A-D ). For 3 out of 4 donors, the load of somatic mutations trended higher in the adenoid-derived antibodies relative to the PBMC-derived antibodies, but this difference only reached statistical significance in donor 2665.

Analysis of the level of SHM within each individual B cell subset revealed that the antibodies derived from the IgG − IgA − CD27 − adenoid B cells contained similar levels of SHM as classical IgG + CD27 + and IgA + CD27 + memory B cells, providing evidence that these B cells are germinal center-experienced ( FIG. 16 B ). In contrast, the majority of antibodies derived from IgG − IgA − CD27 − peripheral blood B cells lacked SHM, indicating a naïve B cell origin. In all 4 donors, the percentage of RSV F-specific IgG − IgA − CD27 − B cells containing SHM was significantly higher in adenoids compared to PBMCs ( FIG. 16 C ). Furthermore, even the small subset of somatically mutated antibodies derived from IgG − IgA − CD27 − peripheral blood B cells contained lower levels of SHM compared to antibodies derived from IgG − IgA − CD27 − adenoid B cells ( FIG. 16 D ). To investigate the IgM and IgD expression profiles of the RSV F-specific IgG − IgA − CD27 − adenoid B cells, the adenoid samples were restained with fluorescently labeled RSV F and a panel of secondary antibodies that included anti-human IgG, IgA, IgM, IgD, and CD27. This analysis revealed a high level of heterogeneity in IgM and IgD expression within this population of RSV F-specific B cells, with some of these B cells expressing only IgM or IgD and others co-expressing both markers ( FIG. 16 E ). These B cells appear to belong to a unique population IgM and/or IgD memory B cells that contain somatic mutations but lack expression of previously described memory B cell markers.

A Higher Proportion of Adenoid-Derived Antibodies Display High Affinity Binding and Potent Neutralizing Activity Compared to PBMC-Derived Antibodies

The apparent (IgG) binding affinities of the antibodies for RSV preF and postF were then measured using biolayer interferometry. The percentage of antibodies that bound exclusively to either preF or postF varied across the 4 donors but was similar between the two compartments within individual donors, with the exception of donor 2849, in which preF-specific antibodies were present at higher frequency in PBMCs compared to adenoid tissue ( FIG. 18 A ). As observed in previous studies, a larger proportion of antibodies bound exclusively to preF (16-65%) than to postF (0-15%), demonstrating that the unique surfaces on preF are likely more immunogenic than those on postF. Although finer epitope mapping is required to better resolve the differences in epitope distribution between the two compartments, the results suggest that the relative immunogenicity of the different antigenic surfaces on RSV F is probably more dependent on the donor repertoire and/or immune history than on the anatomical site of B cell activation ( FIG. 18 A ).

In 3 out of 4 donors, a higher proportion of RSV F-specific antibodies isolated from adenoids bound with medium to high affinity to preF (apparent K D <5.0 nM) compared to antibodies derived from RSV F-reactive peripheral blood B cells ( FIG. 18 B ). For example, 70% of the adenoid-derived antibodies cloned from donor 2666 displayed medium to high binding affinity to preF compared to only about 30% of the PBMC-derived antibodies. This result, combined with the observation that two additional donors had detectable RSV F-specific B cell responses in adenoid tissue but not in peripheral blood ( FIG. 13 B ), suggests that the mucosal B cell response to RSV may be more robust than the corresponding systemic B cell response.

Next, the antibodies were tested for neutralizing activity against RSV-A2 using a previously described luciferase-based assay. 14% to 36% of the adenoid-derived antibodies and 0% to 26% of the PBMC-derived antibodies showed detectable neutralizing activity (IC 50 <25 μg/mL) ( FIG. 19 A ). In all donors, less than 20% of antibodies from both compartments showed highly potent neutralizing activity (IC 50 <0.05 μg/mL), which is lower than that observed for three previously characterized healthy adult donors, in which 19-38% of isolated antibodies neutralized with high potency. The low fraction of highly potent neutralizing antibodies may be due to the young age of these donors, some of which have likely only experienced a single RSV infection. Consistent with this explanation, the antibody panel isolated from the oldest donor (donor 2635) contained the highest proportion of highly potent antibodies ( FIG. 19 A ).

Consistent with the binding analysis, for 3 out of 4 donors, a larger proportion of adenoid-derived antibodies showed neutralizing activity compared to PBMC-derived antibodies ( FIG. 19 A ). For example, for donor 2665, approximately 15% of adenoid-derived antibodies neutralized with an IC 50 ≤25 pg/mL whereas none of the PBMC-derived antibodies showed detectable activity at this concentration. Analysis of the relationship between preF- and postF binding activity and neutralization potency revealed that 50-60% of preF-specific antibodies isolated from both adenoids and PBMCs showed neutralizing activity compared to only 0-8% of postF-specific antibodies and 10-12% of conformation-independent antibodies ( FIG. 19 B ). Importantly, greater than 90% of highly potent antibodies (IC 50 <0.05 pg/mL) isolated from both compartments bound exclusively to preF. The antibody characteristics for antibodies derived from adenoid tissue and PBMCs are shown in Tables 6 and 7, respectively.

Finally, the relationship between memory B cell subset and neutralizing activity was analyzed. Approximately 90% of the PBMC-derived neutralizing antibodies originated from only three B cell subsets (IgG + CD27 + , IgG + CD27 − , and IgG − IgA − CD27 + B cells). In contrast, the adenoid-derived neutralizing antibodies were more evenly distributed across the six different memory B cell populations, with the largest proportion (25%) originating from the atypical IgG − IgA − CD27 − memory B cell subset ( FIG. 19 C ). The antibodies isolated from this atypical memory B cell subset showed similar apparent binding affinities and neutralization potencies compared to the antibodies derived from other memory B cell subsets. These findings demonstrate that 1) adenoid tissue contains a larger proportion of high affinity neutralizing antibodies compared to peripheral blood, 2) a relatively large fraction of RSV F-specific adenoid-derived neutralizing antibodies originate from atypical memory B cells, and 3) the vast majority of neutralizing antibodies isolated from both compartments target epitopes exclusively expressed on preF.

TABLE 6

Summary of antibody characteristics for antibodies isolated from adenoid tissue

Neutralization VH VL

RSV RSV IC50 (RSV PSR VH VL Protein Protein

Name Donor preF KD postF KD subtype A) Specificitiy score Germline Germline Muts Muts

ADI-36669 2635 1.09E−09 N.B. 0.02 preF 0.01 VH1-46 VK1-17 11 1

ADI-36670 2635 7.49E−10 N.B. 0.01 preF 0.01 VH1-69 VK3-15 17 5

ADI-36671 2635 7.28E−10 N.B. 0.01 preF 0.05 VH3-11 VL1-40 11 5

ADI-36672 2635 7.03E−10 N.B. 0.02 preF 0.07 VH3-11 VL1-40 13 6

ADI-36674 2635 7.45E−10 N.B. 0.01 preF 0.01 VH3-21 VL1-40 9 8

ADI-36677 2635 5.40E−10 N.B. 0.02 preF 0.05 VH3-48 VK1-33 8 6

ADI-36679 2635 8.78E−10 N.B. 0.01 preF 0.10 VH5-51 VK1-33 13 12

ADI-36680 2635 7.19E−10 N.B. 0.01 preF 0.10 VH5-51 VK3-15 10 10

ADI-36681 2635 1.20E−09 N.B. 0.01 preF 0.08 VH5-51 VK3-15 8 9

ADI-41144 2635 9.40E−10 7.59E−10 0.37 Both 0.52 VH1-2 VK1-16 14 7

ADI-41145 2635 3.18505E−09 8.14745E−10 >25 Both 0.24 VH4-59 VK1-39 4 3

ADI-41146 2635 4.44E−09 7.46E−10 >25 Both 0.23 VH5-51 VK1-12 14 7

ADI-41147 2635 4.6744E−10 N.B. 0.06 preF 0.21 VH3-11 VL1-40 10 7

ADI-41149 2635 4.34E−09 8.57E−10 >25 Both 0.16 VH3-33 VK3-15 6 6

ADI-41153 2635 9.27936E−10 4.45077E−10 >25 Both 0.14 VH3-21 VK1-39 17 12

ADI-41154 2635 4.63E−09 1.35E−09 >25 Both 0.14 VH4-34 VK1-39 9 7

ADI-41155 2635 3.51668E−09 4.77633E−10 >25 Both 0.13 VH4-39 VL1-47 10 5

ADI-41156 2635 N.B. 1.69623E−09 >25 PostF 0.133957365 VH3-48 VK1-39 4 9

ADI-41157 2635 5.07E−10 N.B. 0.22 preF 0.13 VH4-59 VL1-47 6 13

ADI-41158 2635 4.48646E−09 N.B. >25 preF 0.13 VH3-48 VK3-15 9 0

ADI-41159 2635 N.B. 9.86775E−09 >25 PostF 0.13 VH5-51 VK1-39 4 4

ADI-41160 2635 2.41078E−09 3.36863E−10 >25 Both 0.13 VH1-69 VL2-14 3 8

ADI-41161 2635 2.53811E−09 3.63868E−10 >25 Both 0.12 VH3-48 VL2-14 12 12

ADI-41162 2635 4.06E−09 7.48E−10 >25 Both 0.12 VH1-69 VK3-20 12 6

ADI-41163 2635 4.65418E−09 6.03726E−10 >25 Both 0.12 VH3-33 VK2-28 14 5

ADI-41164 2635 N.B. 9.61753E−10 >25 PostF 0.12 VH3-48 VK1-5 10 14

ADI-41165 2635 2.40E−09 N.B. >25 preF 0.11 VH5-51 VK1-33 0 0

ADI-41166 2635 3.15262E−09 4.40318E−10 >25 Both 0.11 VH1-2 VL2-14 19 12

ADI-41168 2635 1.33E−07 N.B. >25 preF 0.11 VH3-30 VL2-14 1 10

ADI-41169 2635 4.94324E−09 1.18611E−09 >25 Both 0.11 VH5-51 VK4-1 13 6

ADI-41170 2635 5.67E−09 2.64E−09 >25 Both 0.11 VH3-23 VK1-5 12 6

ADI-41171 2635 9.80E−09 4.26E−09 >25 Both 0.11 VH4-31 VK3-20 17 9

ADI-41172 2635 3.05696E−09 7.48831E−10 >25 Both 0.11 VH3-64D VK4-1 10 3

ADI-41173 2635 3.15494E−10 2.93512E−10 0.08 Both 0.11 VH1-69 VK1-17 9 3

ADI-41174 2635 N.B. 7.51319E−10 >25 PostF 0.11 VH1-18 VL3-25 11 6

ADI-41175 2635 4.25E−09 1.07E−09 >25 Both 0.10 VH3-33 VK2-28 7 2

ADI-41176 2635 N.B. 4.07E−09 >25 PostF 0.10 VH4-39 VK1-27 13 6

ADI-41177 2635 8.37277E−10 N.B. >25 preF 0.10 VH1-2 VL1-44 5 4

ADI-41178 2635 1.71747E−09 6.01837E−10 >25 Both 0.10 VH1-2 VK3-15 3 0

ADI-41179 2635 9.48366E−10 3.4151E−10 >25 Both 0.10 VH1-69 VL2-11 9 19

ADI-41180 2635 4.70488E−10 N.B. 0.07 preF 0.10 VH3-11 VL1-40 8 9

ADI-41181 2635 1.95174E−09 9.35655E−10 >25 Both 0.10 VH1-69 VL2-14 7 8

ADI-41182 2635 2.5543E−09 4.62114E−10 >25 Both 0.10 VH5-51 VK3-15 6 6

ADI-41183 2635 4.08E−09 1.00E−09 >25 Both 0.10 VH4-34 VK1-39 15 13

ADI-41184 2635 2.84503E−09 5.31986E−10 >25 Both 0.10 VH3-23 VK1-39 7 5

ADI-41185 2635 3.22683E−9 8.08927E−10 >25 Both 0.10 VH4-34 VK3-20 5 6

ADI-41186 2635 3.01027E−09 7.03469E−10 >25 Both 0.10 VH5-51 VK3-15 4 5

ADI-41188 2635 2.23985E−10 N.B. 0.15 preF 0.10 VH4-34 VL1-40 8 12

ADI-41189 2635 2.86473E−09 6.07729E−10 >25 Both 0.10 VH3-21 VL1-40 4 1

ADI-41190 2635 2.29E−09 9.71E−10 >25 Both 0.08 VH1-3 VK3-20 9 5

ADI-41191 2635 5.01606E−10 N.B. 0.07 preF 0.08 VH1-18 VK2-30 8 6

ADI-41192 2635 3.38603E−09 5.89066E−10 >25 Both 0.07 VH1-18 VK1-39 12 3

ADI-41193 2635 7.40214E−10 N.B. 0.07 preF 0.07 VH3-11 VL1-40 13 8

ADI-41194 2635 N.B. 1.16E−09 >25 PostF 0.07 VH4-31 VK3-20 10 7

ADI-41196 2635 2.9157E−09 5.95141E−10 >25 Both 0.07 VH3-23 VK1-39 12 3

ADI-41197 2635 7.95E−10 5.31E−10 0.27 Both 0.07 VH1-2 VK1-39 12 5

ADI-41198 2635 7.56E−10 N.B. 0.32 preF 0.06 VH3-43 VK1-33 18 12

ADI-41199 2635 1.73E−09 N.B. 0.23 preF 0.06 VH3-11 VK3-15 7 24

ADI-41200 2635 3.34299E−10 3.18362E−10 >25 Both 0.05 VH3-23 VK2-28 14 9

ADI-41201 2635 3.82297E−09 6.37241E−10 >25 Both 0.05 VH3-48 VK3-11 15 9

ADI-41202 2635 1.12088E−09 3.32852E−10 >25 Both 0.05 VH1-69 VL2-11 9 19

ADI-41203 2635 3.99236E−10 N.B. 0.01 preF 0.05 VH5-51 VK3-15 9 10

ADI-41204 2635 5.44567E−10 N.B. 0.06 preF 0.04 VH3-21 VL1-40 3 3

ADI-41205 2635 1.16405E−09 5.3591E−10 >25 Both 0.04 VH4-4 VK4-1 3 6

ADI-41206 2635 4.09075E−10 N.B. 0.07 preF 0.04 VH3-21 VL1-40 11 10

ADI-41207 2635 2.53175E−09 4.37767E−10 >25 Both 0.04 VH2-70 VL2-11 3 13

ADI-41208 2635 4.83434E−10 N.B. 0.08 preF 0.04 VH3-11 VL1-40 11 7

ADI-41209 2635 1.32E−09 1.59E−09 2.97 Both 0.03 VH4-34 VK2-28 11 3

ADI-41210 2635 4.70023E−10 N.B. 0.10 preF 0.02 VH1-18 VK2-30 7 4

ADI-41212 2635 3.17532E−09 4.00134E−10 >25 Both 0.02 VH1-2 VL2-14 11 13

ADI-41213 2635 3.4719E−09 5.76926E−10 >25 Both 0.02 VH3-53 VL3-1 4 2

ADI-41214 2635 5.6989E−09 1.01699E−09 >25 Both 0.01 VH3-7 VK1-39 4 5

ADI-41215 2635 4.37E−10 5.63E−10 0.32 Both 0.01 VH3-20 VL2-23 3 10

ADI-41216 2635 9.03E−10 N.B. 0.19 preF 0.01 VH3-11 VL1-40 9 8

ADI-41217 2635 4.88862E−10 N.B. 0.04 preF 0.01 VH3-21 VL1-40 7 5

ADI-41218 2635 N.B. 7.28659E−10 >25 PostF 0.01 VH1-18 VL1-40 10 7

ADI-41219 2635 N.B. 1.28064E−09 >25 PostF 0.01 VH3-48 VK1-39 7 4

ADI-41221 2635 2.98426E−10 3.16654E−10 0.04 Both 0.01 VH3-21 VL2-11 8 18

ADI-41222 2635 4.30995E−10 N.B. 0.02 preF 0.01 VH3-30 VL3-21 10 11

ADI-41223 2635 N.B. 1.80931E−09 >25 PostF 0.00 VH3-30 VL2-14 6 11

ADI-41224 2635 5.24E−10 5.58E−10 0.13 Both 0.00 VH3-49 VL6-57 7 5

ADI-41225 2635 4.15E−09 7.33E−10 >25 Both 0.00 VH3-11 VK1-5 11 8

ADI-41226 2635 8.20E−10 N.B. 0.15 preF 0.00 VH3-11 VL1-40 15 2

ADI-41227 2635 4.62E−09 N.B. >25 preF 0.00 VH1-69 VL1-36 19 0

ADI-41228 2635 4.86239E−09 6.1786E−10 >25 Both 0.00 VH4-59 VL2-14 6 3

ADI-41229 2635 1.14E−09 7.08E−10 0.07 Both 0.00 VH3-30 VK1-33 10 3

ADI-41230 2635 1.83E−09 4.07E−10 24.10 Both 0.00 VH5-51 VL6-57 11 3

ADI-41231 2635 3.05E−09 4.26E−10 >25 Both 0.00 VH5-51 VL6-57 14 8

ADI-41232 2635 7.05E−10 N.B. 0.03 preF 0.00 VH1-18 VK2-30 6 1

ADI-41233 2635 1.06E−09 N.B. 0.15 preF 0.00 VH3-11 VL1-40 5 3

ADI-41234 2635 1.46E−09 N.B. 0.10 preF 0.00 VH3-30 VK2-28 47 4

ADI-41235 2635 4.72E−09 3.24E−09 >25 Both 0.00 VH4-34 VL1-40 8 7

ADI-41236 2635 N.B. 6.13E−08 >25 PostF 0.00 VH3-11 VL1-40 7 14

ADI-41237 2635 7.94E−10 N.B. 0.04 preF 0.00 VH3-11 VL1-40 5 3

ADI-41238 2635 1.03E−09 N.B. 0.13 preF 0.00 VH3-11 VL1-40 5 6

ADI-41239 2635 4.25E−09 1.47E−09 >25 Both 0.00 VH2-5 VK2-28 6 1

ADI-41240 2635 2.15E−09 1.20E−09 >25 Both 0.00 VH4-34 VK1-5 13 10

ADI-41241 2635 3.84E−09 9.27E−10 18.76 Both 0.00 VH1-2 VK1-39 4 6

ADI-41242 2635 4.18E−09 9.07E−10 >25 Both 0.00 VH3-33 VK2-28 12 2

ADI-41243 2635 3.55E−09 4.18E−10 >25 Both 0.00 VH5-51 VL6-57 9 4

ADI-41244 2635 N.B. 8.43E−10 >25 PostF 0.00 VH3-53 VK4-1 7 6

ADI-41245 2635 7.75E−10 N.B. 0.71 preF 0.00 VH3-11 VL1-40 8 2

ADI-41246 2635 3.07945E−09 N.B. >25 preF 0.00 VH4-59 VK3-20 4 6

ADI-41247 2635 2.76078E−09 1.0202E−09 >25 Both 0.00 VH1-2 VL6-57 10 1

ADI-41248 2635 3.35413E−09 3.91839E−10 >25 Both 0.00 VH3-33 VK1-39 7 5

ADI-41249 2635 3.91497E−10 N.B. 0.01 preF 0.00 VH5-51 VK1-33 14 4

ADI-41250 2635 7.30505E−10 5.04204E−10 >25 Both 0.00 VH4-34 VL2-14 10 8

ADI-41251 2635 5.92669E−10 N.B. 0.11 preF 0.00 VH3-11 VL1-40 5 2

ADI-41252 2635 1.3715E−09 1.00354E−09 >25 Both 0.00 VH5-51 VK1-33 11 2

ADI-41253 2635 1.11084E−09 N.B. 0.03 preF 0.00 VH4-39 VK3-20 19 8

ADI-41254 2635 7.75513E−10 N.B. >25 preF 0.00 VH3-48 VL1-44 8 8

ADI-41255 2635 2.04133E−09 1.54027E−09 >25 Both 0.00 VH3-23 VK3-15 6 3

ADI-41256 2635 3.53762E−10 N.B. 0.02 preF 0.00 VH1-69 VK2-30 18 3

ADI-41257 2635 3.81012E−09 N.B. >25 preF 0.00 VH1-69 VK1-39 10 6

ADI-41258 2635 9.68014E−10 N.B. >25 preF 0.00 VH3-23 VL3-25 12 2

ADI-41259 2635 3.35934E−10 N.B. 0.02 preF 0.00 VH3-11 VK2-30 9 8

ADI-41261 2665 3.08217E−09 1.66794E−09 >25 Both 0.33 VH1-69 VK3-20 7 0

ADI-41263 2665 2.90427E−09 3.45081E−10 >25 Both 0.25 VH1-46 VL6-57 13 5

ADI-41264 2665 N.B. 4.83588E−10 >25 PostF 0.15 VH3-15 VL3-10 9 13

ADI-41265 2665 1.50426E−08 3.0791E−09 >25 Both 0.15 VH5-51 VL1-51 15 6

ADI-41266 2665 4.05839E−09 N.B. >25 preF 0.14 VH6-1 VL3-21 0 11

ADI-41267 2665 1.0722E−08 1.09048E−08 >25 Both 0.12 VH4-4 VL3-1 6 10

ADI-41268 2665 5.80544E−10 N.B. 0.176867623 preF 0.11 VH3-21 VL2-14 12 7

ADI-41270 2665 4.91907E−09 6.17282E−10 >25 Both 0.11 VH3-30-3 VL2-23 5 5

ADI-41271 2665 N.B. 3.11283E−09 >25 PostF 0.11 VH6-1 VK4-1 2 3

ADI-41273 2665 3.06182E−09 1.17234E−09 >25 Both 0.11 VH3-48 VL2-11 17 12

ADI-41274 2665 4.79702E−10 N.B. 0.109081031 preF 0.10 VH3-21 VL1-40 11 10

ADI-41275 2665 5.74247E−09 1.32887E−09 >25 Both 0.10 VH3-21 VK2-28 14 7

ADI-41276 2665 N.B. 3.14914E−09 >25 PostF 0.10 VH3-49 VK3-20 7 2

ADI-41277 2665 3.59859E−09 7.80097E−10 >25 Both 0.10 VH4-4 VK1-39 12 6

ADI-41278 2665 1.28256E−09 4.82496E−10 >25 Both 0.10 VH2-70D VK1-39 7 8

ADI-41279 2665 5.04148E−08 4.78337E−08 >25 Both 0.10 VH5-51 VL1-40 16 10

ADI-41280 2665 3.62407E−09 4.82968E−10 >25 Both 0.10 VH4-59 VK3-20 8 8

ADI-41281 2665 6.69584E−09 1.57901E−09 >25 Both 0.10 VH1-3 VK1-39 18 12

ADI-41282 2665 3.24641E−09 1.25067E−09 >25 Both 0.10 VH3-30-3 VK3-20 11 9

ADI-41283 2665 2.74028E−08 7.95247E−09 >25 Both 0.10 VH2-5 VK1-39 4 14

ADI-41284 2665 3.05821E−09 5.47248E−10 >25 Both 0.10 VH3-15 VL1-51 9 3

ADI-41285 2665 5.11231E−10 4.12147E−10 >25 Both 0.10 VH1-69 VL1-47 12 3

ADI-41286 2665 7.59591E−09 5.48535E−09 >25 Both 0.10 VH1-18 VK1-12 4 6

ADI-41287 2665 3.22264E−09 5.97933E−10 5.845176257 Both 0.09 VH3-9 VL2-11 10 4

ADI-41288 2665 8.99143E−09 N.B. >25 preF 0.08 VH3-23 VK3-20 14 12

ADI-41289 2665 N.B. 8.81474E−10 >25 PostF 0.08 VH5-51 VL2-23 8 10

ADI-41291 2665 2.9847E−09 1.20178E−09 >25 Both 0.07 VH4-34 VK1-39 16 9

ADI-41292 2665 8.83038E−07 1.94972E−07 >25 Both 0.06 VH3-30 VK1-5 10 12

ADI-41293 2665 4.95631E−10 4.10968E−10 0.159400369 Both 0.05 VH4-30-4 VK3-20 6 6

ADI-41294 2665 5.11755E−10 N.B. 0.080516504 preF 0.05 VH3-48 VL2-8 10 9

ADI-41296 2665 3.35264E−09 N.B. >25 preF 0.04 VH5-51 VL3-25 20 19

ADI-41297 2665 3.90841E−09 6.27923E−10 >25 Both 0.04 VH1-69 VL2-14 5 6

ADI-41299 2665 3.48237E−09 2.24822E−09 >25 Both 0.04 VH3-30 VL2-23 14 12

ADI-41302 2665 6.54219E−10 N.B. 0.006 preF 0.03 VH3-30 VL2-8 10 7

ADI-41303 2665 2.95589E−09 9.43837E−10 >25 Both 0.03 VH3-23 VK3-20 18 14

ADI-41304 2665 3.37926E−10 3.30067E−10 >25 Both 0.03 VH4-30-4 VL1-44 9 9

ADI-41305 2665 3.63645E−09 4.31019E−10 >25 Both 0.03 VH4-31 VK3-20 7 4

ADI-41306 2665 4.61555E−10 4.54221E−10 0.173227379 Both 0.02 VH4-30-4 VK3-11 21 10

ADI-41307 2665 2.98694E−09 8.29508E−10 >25 Both 0.02 VH3-21 VK3-15 15 14

ADI-41308 2665 4.00249E−09 5.18915E−10 >25 Both 0.02 VH6-1 VL2-14 4 15

ADI-41309 2665 4.33574E−09 1.36177E−09 >25 Both 0.02 VH4-30-4 VK3-20 8 4

ADI-41310 2665 3.3197E−09 N.B. >25 preF 0.02 VH5-51 VL3-25 18 22

ADI-41311 2665 7.53938E−10 5.24E−10 >25 Both 0.01 VH2-70 VK1-39 7 8

ADI-41312 2665 3.37922E−09 8.56857E−10 >25 Both 0.01 VH4-4 VL1-44 8 2

ADI-41313 2665 4.54784E−10 3.41756E−10 >25 Both 0.01 VH1-18 VL3-9 11 13

ADI-41314 2665 2.40926E−09 4.14355E−10 >25 Both 0.01 VH1-69 VL3-25 13 18

ADI-41315 2665 2.93399E−09 1.0343E−09 >25 Both 0.01 VH4-59 VK3-20 8 5

ADI-41316 2665 3.73659E−09 1.04515E−09 >25 Both 0.01 VH3-30 VK3-15 9 5

ADI-41317 2665 4.81624E−08 N.B. 4.657687235 preF 0.01 VH3-7 VL1-40 12 11

ADI-41318 2665 4.26427E−07 3.53944E−08 >25 Both 0.01 VH1-69 VK1-13 16 9

ADI-41319 2665 4.4099E−09 5.86603E−10 >25 Both 0.01 VH4-30-4 VK3-20 4 4

ADI-41320 2665 3.20131E−09 N.B. >25 preF 0.01 VH5-51 VL3-25 24 18

ADI-41322 2665 2.98155E−09 N.B. >25 preF 0.00 VH1-69 VK1-12 9 3

ADI-41323 2665 1.94986E−09 3.30643E−10 >25 Both 0.00 VH3-20 VL6-57 10 5

ADI-41324 2665 2.4749E−09 4.26392E−10 >25 Both 0.00 VH3-66 VK3-20 4 6

ADI-41340 2665 3.50828E−09 N.B. >25 preF 0.00 VH1-69 VL2-14 18 11

ADI-41341 2665 2.83245E−09 1.96942E−09 >25 Both 0.00 VH1-69 VL1-51 6 9

ADI-41342 2665 3.99333E−09 5.90775E−10 >25 Both 0.00 VH1-69 VK3-20 9 7

ADI-41343 2665 7.21165E−10 N.B. 0.177309561 preF 0.00 VH3-21 VL1-40 5 3

ADI-41344 2665 4.94249E−10 N.B. 0.063680457 preF 0.00 VH3-21 VL1-40 7 4

ADI-41345 2665 2.28687E−09 3.48826E−10 >25 Both 0.00 VH5-51 VL6-57 7 2

ADI-41346 2665 1.88377E−09 2.67433E−10 >25 Both 0.00 VH5-51 VL6-57 15 9

ADI-41347 2665 2.60039E−09 5.2114E−10 >25 Both 0.00 VH4-4 VK2-28 11 5

ADI-41348 2665 4.75842E−10 4.3847E−10 0.076469111 Both 0.00 VH4-31 VK1-39 3 9

ADI-41349 2665 6.24824E−09 >25 Both 0.00 VH3-49 VK1-33 12 8

ADI-41350 2665 N.B. 6.01842E−10 >25 PostF 0.00 VH3-23 VL2-14 4 9

ADI-41351 2665 8.86433E−10 N.B. 0.148889821 preF 0.00 VH3-64 VK3-15 15 3

ADI-41352 2665 3.35674E−09 N.B. >25 preF 0.00 VH3-48 VK4-1 4 0

ADI-41353 2665 3.90918E−09 N.B. >25 preF 0.00 VH5-51 VL3-25 19 17

ADI-41354 2665 7.71337E−10 4.28593E−10 >25 Both 0.00 VH3-23 VK1-33 2 19

ADI-41355 2665 3.84279E−09 1.17814E−09 >25 Both 0.00 VH3-11 VL3-21 10 11

ADI-41356 2665 7.24816E−10 N.B. 0.115429214 preF 0.00 VH1-8 VL3-1 4 7

ADI-41357 2665 3.30683E−09 N.B. >25 preF 0.00 VH3-48 VK1-16 7 4

ADI-41358 2665 8.64199E−10 N.B. 0.388841883 preF 0.00 VH3-21 VL1-40 5 4

ADI-41359 2665 5.27247E−10 N.B. >25 preF 0.00 VH3-21 VL1-40 4 4

ADI-41360 2665 2.45821E−09 3.58127E−10 >25 Both 0.00 VH3-48 VL6-57 11 1

ADI-41361 2665 N.B. 3.8252E−10 2.539820038 PostF 0.00 VH3-30 VK3-15 8 3

ADI-41362 2665 3.37246E−09 N.B. 0.910656137 preF 0.00 VH3-7 VK1-33 14 11

ADI-41363 2665 1.84993E−09 N.B. 0.143419355 preF 0.00 VH1-69 VK1-33 5 6

ADI-41364 2665 1.31503E−09 N.B. 0.140467535 preF 0.00 VH1-2 VL2-23 17 6

ADI-41365 2665 2.87064E−09 2.22411E−09 >25 Both 0.00 VH3-11 VL1-40 7 8

ADI-41366 2665 1.79472E−09 2.78051E−10 >25 Both 0.00 VH5-51 VL6-57 10 8

ADI-41367 2665 1.75638E−08 4.7231E−09 >25 Both 0.00 VH1-3 VL2-14 19 13

ADI-41368 2665 3.07672E−09 8.77542E−10 >25 Both 0.00 VH3-30 VK1-5 14 9

ADI-41369 2665 6.84843E−10 3.07855E−10 >25 Both 0.00 VH3-30 VL6-57 6 4

ADI-41370 2665 5.58964E−09 1.63921E−09 >25 Both 0.00 VH3-21 VL3-25 6 6

ADI-41371 2665 2.96473E−09 5.42686E−10 >25 Both 0.00 VH4-30-4 VK3-20 14 11

ADI-41372 2665 2.47619E−09 4.2465E−10 >25 Both 0.00 VH1-69 VL3-25 8 19

ADI-41373 2665 3.71092E−09 1.18174E−09 >25 Both 0.00 VH3-11 VL1-40 15 7

ADI-41374 2665 1.38715E−09 3.69047E−10 >25 Both 0.00 VH1-69 VK1-33 17 9

ADI-41375 2665 2.96439E−09 1.01798E−09 >25 Both 0.00 VH3-30 VK1-13 8 8

ADI-41376 2665 4.15159E−09 7.0539E−10 >25 Both 0.00 VH3-30 VK3-15 8 4

ADI-41377 2665 1.73768E−09 N.B. 0.239614261 preF 0.00 VH6-1 VL3-21 11 15

ADI-41378 2665 2.98284E−09 7.38719E−10 >25 Both 0.00 VH4-4 VK1-39 5 10

ADI-41379 2665 N.B. 1.10788E−09 >25 PostF 0.00 VH5-51 VK1-33 5 6

ADI-41380 2665 2.56169E−10 N.B. 0.054916106 preF 0.00 VH5-51 VK1-33 0 4

ADI-41381 2665 2.60472E−09 1.33733E−09 >25 Both 0.00 VH4-30-4 VK3-20 13 5

ADI-41382 2666 4.91343E−10 N.B. 0.02 preF 0.00 VH3-9 VK3-15 10 2

ADI-41384 2666 3.45299E−09 5.63124E−10 >25 Both 0.20 VH1-69 VK3-20 10 7

ADI-41385 2666 4.52281E−09 6.00686E−10 >25 Both 0.10 VH3-33 VL1-40 3 2

ADI-41386 2666 4.03244E−10 N.B. >25 preF 0.10 VH1-2 VL1-44 11 7

ADI-41389 2666 2.58276E−09 5.12803E−10 >25 Both 0.10 VH3-30-3 VL3-25 7 1

ADI-41390 2666 6.40545E−10 N.B. 0.62 preF 0.10 VH3-21 VL1-40 7 4

ADI-41391 2666 8.82233E−10 4.78533E−10 >25 Both 0.10 VH4-59 VL2-14 3 5

ADI-41392 2666 3.29102E−10 3.58725E−10 0.18 Both 0.10 VH3-30-3 VL2-14 14 8

ADI-41393 2666 1.66525E−09 2.46585E−10 >25 Both 0.10 VH5-51 VL6-57 2 3

ADI-41394 2666 3.06807E−09 N.B. >25 preF 0.10 VH1-69 VL4-60 11 9

ADI-41396 2666 5.1704E−10 N.B. 1.37 preF 0.10 VH3-21 VL1-40 9 3

ADI-41397 2666 5.81313E−10 N.B. 0.09 preF 0.10 VH3-21 VL1-40 10 2

ADI-41398 2666 6.00144E−10 N.B. 0.17 preF 0.09 VH1-18 VK2-30 1 4

ADI-41399 2666 3.14259E−09 N.B. >25 preF 0.09 VH1-3 VL2-14 3 5

ADI-41400 2666 N.B. 5.47444E−10 >25 PostF 0.09 VH3-48 VK1-5 8 4

ADI-41401 2666 3.21615E−09 N.B. >25 preF 0.07 VH3-9 VK1-39 5 5

ADI-41403 2666 3.04427E−09 8.41083E−10 >25 Both 0.04 VH3-21 VK2-28 9 3

ADI-41404 2666 4.73759E−08 1.3574E−08 >25 Both 0.04 VH1-69 VK3-20 8 3

ADI-41405 2666 2.72169E−09 4.58099E−10 >25 Both 0.02 VH3-48 VK3-11 9 2

ADI-41406 2666 N.B. 5.71343E−10 >25 PostF 0.02 VH3-23 VK1-16 8 6

ADI-41407 2666 2.08406E−09 3.71284E−10 >25 Both 0.01 VH3-23 VK1-27 9 7

ADI-41408 2666 2.13579E−09 N.B. >25 preF 0.00 VH5-51 VK1-33 9 7

ADI-41409 2666 6.26652E−10 N.B. 0.29 preF 0.00 VH1-18 VK2-30 4 2

ADI-41414 2666 2.70176E−09 1.1037E−09 >25 Both 0.00 VH3-66 VK1-5 14 4

ADI-41415 2666 1.08103E−09 6.43742E−10 >25 Both 0.11 VH2-70D VK1-39 9 10

ADI-41416 2666 4.43792E−10 N.B. 0.05 preF 0.10 VH3-21 VL1-40 8 5

ADI-41417 2666 9.19338E−10 N.B. 0.71 preF 0.10 VH3-21 VL1-40 3 2

ADI-41418 2666 1.58304E−09 3.41314E−10 >25 Both 0.10 VH3-15 VL3-10 13 5

ADI-41419 2666 3.0463E−10 N.B. 0.01 preF 0.10 VH3-9 VL2-14 4 6

ADI-41420 2666 N.B. 1.09885E−07 >25 PostF 0.10 VH3-30-3 VL2-18 0 0

ADI-41421 2666 2.51681E−09 N.B. 4.78 preF 0.10 VH1-18 VL3-10 18 4

ADI-41423 2666 5.86859E−08 N.B. >25 preF 0.10 VH3-21 VL2-14 0 1

ADI-41424 2666 7.44001E−10 N.B. 0.28 preF 0.00 VH1-18 VK2-30 14 13

ADI-41425 2666 1.13708E−09 4.96097E−10 >25 Both 0.00 VH2-70 VK1-39 13 9

ADI-41427 2666 2.69701E−09 9.17353E−10 >25 Both 0.21 VH4-59 VL2-14 5 1

ADI-41429 2666 3.61957E−09 1.00206E−09 >25 Both 0.10 VH1-69 VL2-14 3 2

ADI-41431 2666 7.44349E−10 3.44594E−10 2.38 Both 0.10 VH1-18 VL1-51 14 7

ADI-41432 2666 2.04914E−09 2.86037E−10 >25 Both 0.10 VH1-69 VL2-11 14 8

ADI-41433 2666 N.B. 1.2267E−09 >25 PostF 0.10 VH3-30 VL2-11 8 4

ADI-41434 2666 6.13319E−10 N.B. >25 preF 0.10 VH3-9 VK3-15 5 3

ADI-41435 2666 N.B. 3.47214E−09 >25 PostF 0.10 VH3-21 VL1-44 6 4

ADI-41436 2666 1.10343E−09 2.3675E−10 >25 Both 0.10 VH3-30-3 VL6-57 11 5

ADI-41437 2666 3.5009E−10 N.B. >25 preF 0.04 VH1-18 VK4-1 13 4

ADI-41438 2666 3.1446E−09 N.B. >25 preF 0.00 VH1-69 VK3-15 22 11

ADI-41439 2666 5.00975E−10 N.B. 0.34 preF 0.00 VH1-18 VK2-30 10 2

ADI-41440 2666 3.18018E−09 1.23422E−09 >25 Both 0.00 VH3-21 VK3-15 8 4

ADI-41441 2666 3.11642E−09 N.B. >25 preF 0.00 VH4-39 VK1-9 12 5

ADI-41442 2666 5.21389E−10 N.B. 0.04 preF 0.00 VH3-9 VK3D-15 3 3

ADI-41443 2666 2.39989E−09 3.73358E−10 >25 Both 0.00 VH3-33 VK2-28 7 7

ADI-41444 2666 3.01394E−09 5.40812E−10 >25 Both 0.00 VH4-30-4 VK1-5 17 10

ADI-41445 2666 3.04263E−09 7.71859E−10 >25 Both 0.19 VH1-69 VK3-20 17 6

ADI-41446 2666 3.60473E−09 7.21955E−10 >25 Both 0.12 VH3-23 VK3-11 10 6

ADI-41447 2666 5.40998E−08 N.B. >25 preF 0.12 VH3-23 VK3-20 4 3

ADI-41448 2666 2.74846E−09 4.28394E−10 >25 Both 0.10 VH1-69 VL2-14 16 12

ADI-41449 2666 5.07579E−10 N.B. 0.16 preF 0.10 VH3-21 VL1-40 10 5

ADI-41450 2666 6.13101E−10 N.B. 0.21 preF 0.10 VH3-21 VL1-40 12 9

ADI-41451 2666 1.82249E−09 1.66981E−09 0.84 Both 0.10 VH3-48 VL3-1 13 16

ADI-41452 2666 3.33249E−09 N.B. >25 preF 0.10 VH1-3 VL2-14 19 6

ADI-41453 2666 2.16827E−09 4.02833E−10 >25 Both 0.10 VH1-8 VL3-9 8 4

ADI-41454 2666 5.87531E−10 N.B. 0.88 preF 0.10 VH1-18 VK2-30 7 4

ADI-41455 2666 1.52555E−09 6.37546E−10 >25 Both 0.08 VH4-30-4 VK3-11 8 1

ADI-41456 2666 1.48371E−09 2.66707E−10 >25 Both 0.08 VH3-74 VL6-57 13 3

ADI-41488 2849 N.B. 6.05E−10 >25 PostF 0.10 VH4-59 VL2-11 12 6

ADI-41489 2849 8.80E−08 N.B. >25 preF 0.10 VH3-30 VK3-15 13 6

ADI-41491 2849 4.39E−10 N.B. >25 preF 0.08 VH3-48 VL3-21 7 4

ADI-41492 2849 1.82E−07 5.48E−08 >25 Both 0.07 VH1-69 VK1-39 11 6

ADI-41493 2849 4.50E−10 3.72E−10 >25 Both 0.06 VH5-51 VL2-8 5 2

ADI-41494 2849 2.61E−09 4.40E−10 >25 Both 0.06 VH3-49 VL2-14 16 7

ADI-41495 2849 7.72E−08 5.73E−08 >25 Both 0.05 VH3-15 VL6-57 12 4

ADI-41496 2849 1.65E−09 1.37E−09 >25 Both 0.04 VH1-8 VL2-23 3 6

ADI-41497 2849 1.44E−09 2.68E−10 >25 Both 0.04 VH3-30 VL3-21 12 7

ADI-41498 2849 1.22E−09 2.20E−10 >25 Both 0.04 VH3-21 VL3-21 13 4

ADI-41499 2849 1.99E−09 2.97E−10 >25 Both 0.04 VH3-43 VL2-11 13 9

ADI-41501 2849 3.21E−09 N.B. >25 preF 0.03 VH1-69 VK4-1 13 4

ADI-41502 2849 1.34E−09 3.08E−10 >25 Both 0.01 VH1-69 VL2-11 12 5

ADI-41503 2849 3.14E−09 4.93E−10 >25 Both 0.01 VH3-23 VL2-14 9 3

ADI-41504 2849 2.80E−09 5.08E−10 >25 Both 0.01 VH4-59 VL1-40 8 3

ADI-41505 2849 2.87E−09 5.23E−10 >25 Both 0.00 VH4-34 VL1-40 11 4

ADI-41507 2849 N.B. 1.40E−07 >25 PostF 0.00 VH2-5 VL1-40 4 5

ADI-41508 2849 4.15E−09 5.55E−10 0.10 Both 0.00 VH1-18 VL3-1 13 6

ADI-41515 2849 3.33E−10 N.B. >25 preF 0.00 VH3-23 VL3-10 13 7

ADI-41516 2849 4.14E−10 N.B. 0.08 preF 0.00 VH4-4 VL1-47 16 7

ADI-41517 2849 5.01E−10 N.B. 0.02 preF 0.00 VH3-23 VL1-40 10 4

ADI-41518 2849 7.76E−10 N.B. >25 preF 0.00 VH3-21 VL1-40 2 0

ADI-41519 2849 9.75E−10 N.B. >25 preF 0.00 VH4-39 VK3-20 15 2

ADI-41520 2849 9.98E−10 N.B. >25 preF 0.00 VH3-20 VK1-39 6 8

ADI-41521 2849 1.68E−09 N.B. >25 preF 0.00 VH3-9 VK3-20 9 11

ADI-41522 2849 2.20E−09 N.B. >25 preF 0.00 VH1-69 VL2-14 10 5

ADI-41523 2849 2.91E−09 N.B. >25 preF 0.00 VH5-51 VK1-39 6 2

ADI-41524 2849 3.18E−09 N.B. >25 preF 0.00 VH3-49 VK2-28 6 3

ADI-41525 2849 N.B. 3.27E−10 >25 PostF 0.00 VH1-69 VL2-14 19 4

ADI-41526 2849 3.01E−10 3.36E−10 >25 Both 0.00 VH1-2 VL1-44 8 6

ADI-41527 2849 7.12E−10 3.37E−10 >25 Both 0.00 VH3-7 VK1-12 4 6

ADI-41528 2849 2.28E−09 3.48E−10 >25 Both 0.00 VH3-30 VL3-1 5 8

ADI-41529 2849 1.03E−09 3.51E−10 >25 Both 0.00 VH1-69 VK3-20 19 7

ADI-41530 2849 1.91E−09 3.55E−10 >25 Both 0.00 VH1-8 VL3-9 10 8

ADI-41531 2849 2.08E−09 3.77E−10 >25 Both 0.00 VH3-23 VK1-33 12 11

ADI-41532 2849 1.92E−09 3.92E−10 >25 Both 0.00 VH5-51 VL1-44 5 3

ADI-41533 2849 1.47E−09 4.23E−10 >25 Both 0.00 VH3-30 VL3-1 10 9

ADI-41534 2849 3.31E−09 4.72E−10 >25 Both 0.00 VH3-30 VL3-1 8 3

ADI-41535 2849 1.93E−09 4.76E−10 >25 Both 0.00 VH2-70D VK1-39 5 6

ADI-41536 2849 3.05E−09 4.76E−10 >25 Both 0.00 VH4-34 VL1-40 10 3

ADI-41537 2849 2.58E−09 4.88E−10 >25 Both 0.00 VH3-23 VK2-28 7 2

ADI-41538 2849 3.44E−09 5.87E−10 >25 Both 0.00 VH3-21 VK4-1 12 4

ADI-41538 2849 3.44E−09 5.87E−10 >25 Both 0.00 VH3-21 VK4-1 12 4

ADI-41539 2849 3.38E−09 6.15E−10 0.18 Both 0.00 VH1-18 VK3-15 6 3

ADI-41540 2849 3.54E−09 6.86E−10 >25 Both 0.00 VH4-34 VK3-20 17 9

ADI-41541 2849 2.47E−09 7.76E−10 >25 Both 0.00 VH2-5 VL3-21 1 2

ADI-41542 2849 N.B. 7.96E−10 0.69 PostF 0.00 VH5-51 VK1-33 9 9

ADI-41543 2849 2.90E−09 7.96E−10 >25 Both 0.00 VH1-2 VK2-28 16 4

ADI-41544 2849 N.B. 8.05E−10 >25 PostF 0.00 VH5-51 VK1-33 6 3

ADI-41545 2849 1.36E−09 8.25E−10 >25 Both 0.00 VH4-59 VL3-21 7 2

ADI-41546 2849 N.B. 1.08E−09 >25 PostF 0.00 VH5-51 VK1-9 4 1

ADI-41547 2849 3.19E−09 1.08E−09 0.05 Both 0.00 VH1-69 VK3-20 11 7

ADI-41548 2849 2.56E−09 1.45E−09 >25 Both 0.00 VH4-4 VK3-15 13 5

ADI-41549 2849 4.08E−10 1.56E−09 >25 Both 0.00 VH3-30 VL2-14 5 2

ADI-41550 2849 2.29E−10 2.57E−08 >25 Both 0.00 VH1-18 VL3-21 10 2

ADI-41551 2849 1.30E−08 2.38E−08 >25 Both 0.00 VH3-74 VL3-1 8 8

ADI-43643 2666 7.66E−08 N.B. >25 preF 0.10 VH3-21 VL1-40 0 0

ADI-43644 2665 2.93206E−08 N.B. >25 preF 0.00 VH3-23 VK3-11 0 0

ADI-43645 2666 8.70E−09 N.B. >25 preF 0.25 VH1-69 VK1-5 0 0

ADI-43646 2635 5.34462E−09 N.B. >25 preF 0 VH3-43D VL2-14 0 1

ADI-43647 2635 N.B. 4.4563E−08 >25 PostF 0 VH3-23 VK1-12 3 0

ADI-43648 2666 N.B. 2.86E−08 >25 PostF 0.10 VH1-8 VL3-9 0 1

TABLE 7

Summary of antibody characteristics for antibodies isolated from PBMCs

VH VL

RSV preF RSV postF Neutralization IC50 PSR VH VL Protein Protein

Name Donor binding KD binding KD (RSV subtype A) Specificiity score Germline Germline Muts Muts

ADI-36673 2635 6.20328E−10 N.B. 0.019954073 preF 0.00 VH3-11 VL1-40 7 5

ADI-36675 2635 8.07354E−10 N.B. 0.006 preF 0.00 VH3-23 VL1-51 10 11

ADI-36676 2635 2.82227E−10 N.B. 0.006 preF 0.00 VH3-30 VL3-21 10 5

ADI-36678 2635 7.16249E−10 N.B. 0.006 preF 0.14 VH3-66 VL3-1 14 15

ADI-41552 2635 3.44465E−09 5.21877E−10 >25 Both 0.39 VH3-48 VK3-11 10 4

ADI-41553 2635 N.B. 8.03693E−10 >25 postF 0.22 VH1-18 VK1-5 7 1

ADI-41554 2635 1.34614E−09 1.07074E−09 >25 Both 0.21 VH3-23 VK1-5 8 7

ADI-41555 2635 5.68885E−09 1.12393E−09 25 Both 0.20 VH4-31 VK3-11 8 7

ADI-41556 2635 N.B. 2.27656E−09 >25 postF 0.19 VH3-21 VK3-15 5 3

ADI-41557 2635 3.08525E−08 8.61139E−08 >25 Both 0.17 VH4-59 VK3-15 11 8

ADI-41558 2635 3.01911E−09 7.00004E−10 >25 Both 0.17 VH3-11 VK3-20 14 5

ADI-41561 2635 3.32537E−09 5.15754E−10 >25 Both 0.14 VH2-5 VK1-12 10 8

ADI-41562 2635 N.B. 6.75971E−10 >25 postF 0.12 VH1-18 VK3-15 20 6

ADI-41563 2635 6.02208E−10 N.B. 0.032327297 preF 0.12 VH4-59 VL1-40 11 11

ADI-41564 2635 4.43977E−09 5.95709E−10 >25 Both 0.12 VH1-69 VK3-20 20 0

ADI-41567 2635 7.16511E−10 N.B. 0.050532702 preF 0.11 VH4-34 VK1-9 12 4

ADI-41568 2635 N.B. 2.0658E−09 >25 postF 0.09 VH4-34 VL3-25 7 4

ADI-41569 2635 3.29786E−09 1.60525E−09 >25 Both 0.08 VH1-69 VK3D-15 10 7

ADI-41570 2635 2.97345E−09 1.1235E−09 25 Both 0.08 VH1-69 VL1-51 11 6

ADI-41571 2635 6.27081E−10 N.B. 0.031530527 preF 0.07 VH3-11 VL1-40 14 10

ADI-41574 2635 N.B. 1.23235E−07 >25 postF 0.02 VH2-5 VK1-5 1 7

ADI-41576 2635 N.B. 1.42548E−09 >25 postF 0.01 VH2-5 VK3-11 9 10

ADI-41578 2635 2.48656E−10 N.B. 0.039833521 preF 0.00 VH3-30 VL3-21 11 12

ADI-41579 2635 4.71437E−10 3.59718E−10 0.208709151 Both 0.00 VH1-69 VL2-14 15 13

ADI-41580 2635 2.98246E−09 1.17422E−09 1.107269577 Both 0.00 VH4-34 VK4-1 10 10

ADI-41581 2635 2.7729E−09 3.60691E−10 >25 Both 0.00 VH7-4-1 VK2-28 10 4

ADI-41582 2635 N.B. 9.11488E−10 >25 postF 0.00 VH4-31 VL3-21 6 8

ADI-41583 2635 6.63714E−10 3.80536E−10 >25 Both 0.00 VH1-69 VK1-33 10 1

ADI-41584 2635 3.08613E−09 N.B. >25 preF 0.00 VH1-2 VL1-40 10 5

ADI-41585 2635 6.13E−10 N.B. 0.064052351 preF 0.00 VH3-11 VL1-40 6 3

ADI-41586 2635 5.37539E−10 7.79176E−10 0.401663761 Both 0.00 VH4-34 VK2-28 9 3

ADI-41587 2635 1.4048E−09 2.08899E−09 0.663851609 Both 0.00 VH4-34 VK2-28 8 5

ADI-41588 2635 3.32826E−09 5.04922E−10 >25 Both 0.00 VH2-5 VL3-1 5 2

ADI-41589 2635 4.20258E−09 N.B. >25 preF 0.00 VH3-23 VK4-1 8 8

ADI-41590 2635 3.0202E−09 N.B. >25 preF 0.00 VH3-11 VK1-39 7 10

ADI-41591 2635 4.25861E−09 N.B. >25 preF 0.00 VH3-11 VL1-40 0 2

ADI-41592 2635 3.73679E−09 4.40201E−10 >25 Both 0.00 VH7-4-1 VL3-1 5 13

ADI-41593 2635 1.8323E−09 5.29992E−10 >25 Both 0.00 VH5-51 VK1-8 4 2

ADI-41594 2635 4.13628E−10 N.B. 0.040569222 preF 0.00 VH3-21 VL1-40 10 4

ADI-41595 2635 7.70076E−10 N.B. 0.047476327 preF 0.00 VH3-30 VK1-33 9 11

ADI-41596 2635 3.04558E−10 4.37255E−10 0.053741113 Both 0.00 VH4-34 VK4-1 6 2

ADI-41597 2635 3.56836E−10 N.B. 0.172508371 preF 0.00 VH4-61 VL3-21 6 3

ADI-41598 2635 4.94657E−10 N.B. 0.174094146 preF 0.00 VH4-59 VK1-39 11 11

ADI-41599 2635 7.90767E−10 4.32706E−10 0.636806381 Both 0.00 VH3-48 VK1-39 16 13

ADI-41600 2635 4.93359E−09 7.54853E−10 >25 Both 0.00 VH3-30 VK1D-12 15 9

ADI-41601 2635 5.02595E−10 N.B. >25 preF 0.00 VH3-11 VL1-40 11 10

ADI-41602 2635 2.85465E−09 4.54781E−10 >25 Both 0.00 VH4-59 VL2-14 7 10

ADI-41603 2635 3.49281E−09 4.89905E−10 >25 Both 0.00 VH3-49 VK3-15 10 6

ADI-41604 2635 1.7801E−08 2.92494E−08 >25 Both 0.00 VH1-2 VK1-33 1 0

ADI-41605 2635 3.18275E−09 5.5033E−10 >25 Both 0.00 VH4-31 VK4-1 8 9

ADI-41606 2635 3.38754E−09 1.02586E−09 >25 Both 0.00 VH4-61 VK1D-12 9 7

ADI-41607 2635 4.24282E−09 7.09182E−10 >25 Both 0.00 VH4-31 VL2-11 7 11

ADI-41608 2635 1.93484E−09 2.85427E−10 >25 Both 0.00 VH5-51 VL6-57 15 3

ADI-41609 2635 2.90676E−08 N.B. >25 preF 0.00 VH1-46 VL1-40 14 10

ADI-41610 2635 N.B. 9.78084E−10 >25 postF 0.00 VH3-30 VK1-39 12 1

ADI-41611 2635 3.08502E−09 6.11386E−10 >25 Both 0.00 VH3-21 VK1-39 6 6

ADI-41626 2665 2.60E−09 8.91E−10 >25 Both 0.17 VH4-4 VK1-39 9 9

ADI-41644 2665 3.03E−09 1.10E−09 >25 Both 0.11 VH4-34 VK3D-15 13 14

ADI-41660 2665 2.94E−09 9.55E−10 >25 Both 0.10 VH1-69 VL1-51 5 1

ADI-41662 2665 5.24E−09 1.21E−09 >25 Both 0.10 VH5-51 VL3-10 14 6

ADI-41664 2665 2.94E−09 8.25E−10 >25 Both 0.10 VH1-18 VL3-21 11 5

ADI-41677 2665 1.28E−09 3.39E−10 >25 Both 0.08 VH2-70 VK1-39 5 12

ADI-41678 2665 2.92E−09 1.17E−09 >25 Both 0.08 VH3-30 VL2-8 5 0

ADI-41690 2665 N.B. 8.78E−09 >25 postF 0.03 VH5-51 VK1-33 8 5

ADI-41701 2665 1.93E−09 2.89E−10 >25 Both 0.01 VH5-51 VL6-57 6 9

ADI-41703 2665 4.20E−09 8.43E−10 >25 Both 0.00 VH4-30-2 VK3-20 6 5

ADI-41720 2665 2.20E−08 1.17E−09 >25 Both 0.00 VH3-33 VK1-5 5 2

ADI-41737 2665 3.58E−09 1.58E−09 >25 Both 0.00 VH4-30-4 VK3-20 9 8

ADI-41743 2665 5.45E−09 1.27E−09 >25 Both 0.00 VH4-30-2 VK3-15 14 4

ADI-41756 2665 2.90E−08 N.B. >25 preF 0.00 VH3-30 VL2-14 8 20

ADI-41768 2666 1.61459E−09 3.38298E−10 >25 Both 0.10 VH3-9 VL6-57 6 6

ADI-41772 2666 7.10105E−10 N.B. 0.04 preF 0.10 VH3-11 VL3-10 12 7

ADI-41778 2666 2.75256E−09 5.04199E−10 >25 Both 0.10 VH3-9 VL2-11 5 4

ADI-41781 2666 3.46456E−09 6.53361E−10 >25 Both 0.07 VH1-18 VK1-27 16 4

ADI-41783 2666 5.42456E−10 N.B. 0.25 preF 0.10 VH1-18 VK2-30 7 0

ADI-41787 2666 1.56237E−09 N.B. 0.38 preF 0.10 VH3-30 VL3-10 7 6

ADI-41788 2666 2.755E−10 N.B. 0.47 preF 0.10 VH1-8 VL3-21 8 1

ADI-41790 2666 3.15261E−09 N.B. >25 preF 0.10 VH1-69 VK3-11 7 6

ADI-41792 2666 2.98373E−08 N.B. >25 preF 0.10 VH3-21 VL1-40 2 1

ADI-41794 2666 3.30922E−09 3.01006E−09 >25 Both 0.10 VH4-34 VL1-51 0 3

ADI-41799 2666 3.27629E−09 1.10141E−09 >25 Both 0.14 VH1-69 VK1-5 17 5

ADI-41800 2849 3.24E−09 N.B. >25 preF 0.40 VH1-2 VL2-14 10 5

ADI-41803 2849 1.99E−09 7.11E−10 >25 Both 0.17 VH4-34 VK1-17 16 6

ADI-41804 2849 3.31E−10 4.36E−10 >25 Both 0.15 VH4-34 VK1-27 11 5

ADI-41805 2849 N.B. 2.00E−09 >25 postF 0.14 VH5-51 VL2-14 4 7

ADI-41807 2849 1.50E−09 1.19E−09 >25 Both 0.14 VH2-70 VK1-39 6 10

ADI-41808 2849 1.39E−08 2.25E−08 >25 Both 0.14 VH1-69 VK1-5 21 7

ADI-41809 2849 2.65E−09 N.B. >25 preF 0.12 VH3-23 VL1-47 9 5

ADI-41810 2849 2.03E−09 N.B. >25 preF 0.11 VH3-30 VK3-15 7 8

ADI-41811 2849 1.64E−09 7.44E−10 >25 Both 0.11 VH6-1 VK3-11 10 7

ADI-41812 2849 3.14E−10 N.B. 0.17 preF 0.11 VH3-21 VL1-40 6 1

ADI-41814 2849 3.39E−09 9.15E−10 >25 Both 0.10 VH2-5 VL1-40 3 13

ADI-41815 2849 3.21E−09 N.B. >25 preF 0.10 VH3-21 VK2-28 9 0

ADI-41816 2849 6.56E−10 N.B. 0.91 preF 0.10 VH1-2 VL3-1 8 2

ADI-41817 2849 6.94E−09 1.58E−08 >25 Both 0.09 VH5-51 VL2-14 7 9

ADI-41818 2849 6.76E−10 3.47E−10 >25 Both 0.03 VH3-66 VK3-20 8 2

ADI-41820 2849 6.49E−08 N.B. >25 preF 0.01 VH3-30 VL7-46 11 4

ADI-41827 2849 1.86E−10 N.B. >25 preF 0.00 VH3-30 VL3-1 10 7

ADI-41828 2849 2.41E−10 N.B. 5.53 preF 0.00 VH3-48 VL3-21 9 0

ADI-41829 2849 2.71E−10 N.B. 0.12 preF 0.00 VH3-21 VL1-40 5 2

ADI-41830 2849 2.90E−10 N.B. 0.12 preF 0.00 VH1-18 VK2-28 13 0

ADI-41831 2849 3.29E−10 N.B. 5.21 preF 0.00 VH3-21 VL1-40 8 3

ADI-41832 2849 6.31E−10 N.B. 0.19 preF 0.00 VH3-23 VK3-20 8 4

ADI-41833 2849 7.23E−10 N.B. 0.02 preF 0.00 VH3-23 VK1-27 7 6

ADI-41834 2849 1.20E−09 N.B. 0.07 preF 0.00 VH3-66 VK1-33 9 5

ADI-41835 2849 1.43E−09 N.B. 0.45 preF 0.00 VH3-23 VL3-1 3 4

ADI-41836 2849 5.74E−09 N.B. >25 preF 0.00 VH1-3 VL1-40 9 8

ADI-41837 2849 7.09E−09 N.B. >25 preF 0.00 VH1-18 VK2-30 4 3

ADI-41838 2849 3.21E−08 N.B. >25 preF 0.00 VH3-30 VL2-14 8 3

ADI-41839 2849 7.88E−09 N.B. >25 preF 0.00 VH3-30 VL3-21 14 2

ADI-41840 2849 3.33E−09 N.B. >25 preF 0.00 VH1-69 VK3-15 17 3

ADI-41841 2849 1.21E−10 2.65E−10 0.04 Both 0.00 VH3-21 VK1-33 6 8

ADI-41842 2849 7.17E−10 4.42E−10 >25 Both 0.00 VH1-8 VK1-39 14 6

ADI-43638 2665 N.B. 9.93404E−09 >25 postF 0.16 VH4-34 VK4-1 0 0

ADI-43639 2635 N.B. 2.32551E−07 >25 postF 0.00 VH7-4-1 VK1-39 0 0

ADI-43640 2665 2.15586E−08 N.B. >25 preF 0.08 VH3-21 VL1-40 0 0

ADI-43641 2665 3.74656E−08 N.B. >25 preF 0.09 VH3-11 VL1-40 0 0

ADI-43642 2635 4.31745E−08 N.B. >25 preF 0.00 VH3-21 VL1-40 0 0

Adenoid- and PBMC-Derived Antibodies Show Similar Levels of Polyreactivity

The specificity of each antibody was assessed using a previously described polyreactivity assay. In healthy adult donors, a relatively large proportion of memory B cell-derived antibodies have been shown to be polyreactive (Tiller, 2007). Consistent with these findings, approximately 35% of antibodies derived from both the adenoid and PBMC samples showed low levels of polyreactivity ( FIG. 20 A ). The percentage of polyreactive clones was relatively similar across the different B cell subsets within each compartment, although the PBMC-derived IgG − IgA − CD27 − B cell population showed a slighter higher proportion of polyreactive clones compared to many of the other B cell subsets ( FIG. 20 B ). A slight enrichment for polyreactive clones was observed among the group of antibodies that bound with weak affinity to RSV F ( FIG. 20 C ). In conclusion, the mucosal and systemic B cell compartments contain a similar proportion of polyreactive clones, with about a third of RSV F-specific B cells in both compartments showing some degree of polyreactivity.

Discussion

A detailed understanding of mucosal and systemic immune responses to natural RSV infection can facilitate the design and evaluation of RSV vaccine candidates. Although previous studies have shown that mucosal antibody responses are important for protection against RSV in both humans and animal models, the specificities and functional activities of these antibodies have remained undefined. Furthermore, the anatomic location(s) and characteristics of RSV-specific memory B cells within mucosa-associated lymphoid tissues have not been thoroughly investigated. By collecting paired adenoid and blood samples from six young children undergoing elective tonsillectomy and using a high-throughput B cell cloning platform, the local and systemic B cell responses to natural RSV infection were analyzed and compared.

RSV F-specific B cell responses were observed in the adenoids of all 6 donors analyzed, whereas such responses were only detected in the peripheral blood samples of 4 of the 6 donors. In addition, in most donors studied, a higher proportion of adenoid-derived antibodies displayed high affinity binding and potent neutralizing activity compared to PBMC-derived antibodies. These results provide evidence that RSV-specific memory B cells are induced and maintained within adenoid tissue and suggest that this local response may be more robust and/or durable than the corresponding systemic response. Hence, adenoidectomy may result in a reduction of local immune competence against RSV, as previously demonstrated by diminished poliovirus-specific antibody levels in nasal secretions from children following tonsillectomy and adenoidectomy (Ogra P. L. (1971) Effect of tonsillectomy and adenoidectomy on nasopharyngeal antibody response to poliovirus. N. Engl. J. Med. 284:59-6).

The adenoids of all donors studied contained a high frequency of RSV F-specific memory B cells that displayed mutated v-regions but were not isotype-switched and lacked expression of the classical memory B cell marker CD27. Although RSV F-specific B cells that displayed this surface phenotype were also present in peripheral blood, the frequency was significantly lower than that observed in adenoid tissue and the majority of these B cells encoded antibodies that lacked somatic mutations. Unlike the tissue-based IgG + CD27 − FCRL4 + memory B cell population that has been previously described in human tonsils, the RSV F-specific IgG − IgA − CD27 − B cells observed in the adenoids of these donors did not express FCRL4 or IgG and were highly heterogeneous with respect to IgM and IgD expression. Previous studies have also described atypical memory B cells in peripheral blood that are isotyped-switched, lack CD27 expression, and display lower levels of SHM compared to their CD27 + counterparts. In contrast to this population, the atypical adenoid-derived memory B cell subset described here shows similar levels of SHM compared to classical IgG + CD27 + memory B cells, suggesting similar antigenic selection characteristics. A single clonal lineage present in both adenoid and peripheral blood of one donor was identified, and the PBMC-derived clone originated from an IgG + CD27 − B cell whereas the adenoid-derived clone originated from an IgG − IgA − CD27 − B cell, suggesting a possible relationship between these two atypical B cell subsets. RSV F-specific IgA + memory B cells were detected in both adenoid and peripheral blood for all donors.

Previous studies have shown that RSV antibodies that bind preF-specific surfaces are generally more potent than those that recognize epitopes expressed on both pre- and post-F or only on postF. Correspondingly, in the 4 young children analyzed here, over 90% of the neutralizing antibodies isolated from both adenoid and peripheral blood recognized epitopes exclusively expressed on preF. The high abundance of preF-specific neutralizing antibodies and near absence of postF-reactive neutralizing antibodies in adenoid tissue suggests that mucosal vaccines the preserve preF-specific antigenic surfaces may induce higher titers of protective antibodies than postF-based vaccines. Although the majority of mucosal vaccines are particle- or vector-based, it has been shown that preF can spontaneously trigger to adopt postF conformation on the viral surface, underscoring the importance of carefully evaluating the antigenic properties of such vaccine candidates. The extensive panel of antibodies described here could be used as reagents to measure the prefusion and postfusion F content of these vaccines.

Collectively, this demonstrates that 1) adenoids can serve as a major induction site for RSV-specific memory B cell responses and that a large proportion of this response is comprised of atypical IgM+ and/or IgD+ memory B cells; 2) the vast majority of adenoid-derived neutralizing antibodies target epitopes exclusively expressed on preF, which supports the development of preF-based mucosal vaccines that boost local responses.

Methods

Sample Collection

Heparinized blood and tonsillar tissue were collected from the patient after a planned therapeutic tonsillectomy for clinical indications (parental consent obtained during a pre-operative visit in accordance with approved IRB). Tonsillar tissue consisted of tonsils (palatine tonsils) and adenoids (pharyngeal tonsils), which together make up Waldeyer's ring.

After collection, tonsillar tissue was mechanically disrupted, e.g., grinding of tissue between the fritted glass at the end of microscope slides or by proteolytic digestion of the tissue typically with pronase, and mucosal lymphoid populations were isolated by standard methods, e.g., ficoll gradient. Several methods exist to recover secreted immunoglobulins from the mucosal surface of the tissue, e.g., Pope earwick or ex vivo culture systems. Peripheral blood was separated to recover plasma and then further fractionated to recover lymphoid cells.

Isolated lymphoid cells from paired tonsillar tissue and blood were used to identify and characterize monoclonal antibodies from single B cells.

Production of RSV F Sorting Probes

PreF (DS-Cav1) and postF (F ΔFP) trimers were produced with a single biotinylated C-terminal AviTag and then coupled to streptavidin-PE or APC, as described previously (Gilman et al, Sci Immunol 2016). Expression vectors containing a C-terminal 6x His-tag-AviTag or a C-terminal Strep-tag II were co-transfected into FreeStyle 293-F cells at a 1:2 ratio for each variant. The protein was purified from the cell supernatant using Ni-nitrilotriacetic acid (NTA) resin to remove trimers lacking the 6x His-tag-AviTag, then purified over StrepTactin resin. The resin was washed to remove trimers containing only one StrepTagII, and the remaining proteins were then biotinylated using birA (Avidity). The biotinylated proteins were separated from excess biotin by size-exclusion chromatography using a Superdex 200 column (GE Healthcare) in PBS.

Single B Cell Sorting

PBMCs and adenoids from young children were stained using anti-human CD19 (APC-Cy7), CD20 (APC-Cy7), CD3 (PerCP-Cy5.5), CD8 (PerCP-Cy5.5), CD14 (PerCP-Cy5.5), CD16 (PerCP-Cy5.5), FcRL4 (PECy7), IgG (BV605), IgA (488), CD27 (BV421), and a mixture of dual-labeled preF and postF tetramers (25 nM each). To determine the percentage of RSV-F specific B cells expressing IgM or IgD, the adenoid samples were stained using human CD19 (APC-Cy7), CD20 (APC-Cy7), CD3 (PerCP-Cy5.5), CD8 (PerCP-Cy5.5), CD14 (PerCP-Cy5.5), CD16 (PerCP-Cy5.5), IgM (PECy7), IgD (BV510), IgG (BV605), IgA (488), CD27 (BV421), and a mixture of dual-labeled preF and postF tetramers (25 nM each). Tetramers were prepared fresh for each experiment, and total B cells binding to the RSV F tetramers were single cell sorted. Single cells were sorted using a BD FACS Aria II (BD Biosciences) into 96-well PCR plates (BioRAD) containing 20 uL/well of lysis buffer [5 uL of 5X first strand cDNA buffer (Invitrogen), 0.625 uL of NP-40 (New England Biolabs), 0.25 uL RNaseOUT (Invitrogen), 1.25 uL dithiothreitol (Invitrogen), and 12.6 uL dH2O]. Plates were immediately stored at −80° C.

Amplification and Cloning of Antibody Variable Genes

Antibody variable genes (IgH, IgK, and IgL) were amplified by reverse transcription PCR and nested PCRs using cocktails of IgG-, IgA-, and IgM-specific primers, as described previously (Tiller et al, J Immunol 2008). The primers used in the second round of PCR contained 40 base pairs of 5′ and 3′ homology to the digested expression vectors, which allowed for cloning by homologous recombination into S. cerevisiae . The lithium acetate method for chemical transformation was used to clone the PCR products into S. cerevisiae (Gietz and Schiestl, Nat Protoc 2007). 10 uL of unpurified heavy chain and light chain PCR product and 200 ng of the digested expression vectors were used per transformation reaction. Following transformation, individual yeast colonies were picked for sequencing and characterization.

Expression and Purification of IgGs

IgGs were expressed in S. cerevisiae cultures grown in 24-well plates, as described previously (Bornholdt et al, Science 2016). After 6 days, the cultures were harvested by centrifugation and IgGs were purified by protein A-affinity chromatography. The bound antibodies were eluted with 200 mM acetic acid/50 mM NaCl (pH 3.5) into ⅛th volume 2 M Hepes (pH 8.0), and buffer-exchanged into PBS (pH 7.0).

Biolayer Interferometry Binding Analysis

IgG binding to preF (DS-Cav1) and postF (F ΔFP) was measured by biolayer interferometry (BLI) using a ForteBio Octet HTX instrument (Pall Life Sciences). For high-throughput K D determination, IgGs were immobilized on anti-human IgG quantitation biosensors (Pall Life Sciences) and exposed to 100 nM antigen in PBS with 0.1% BSA (PBSF) for an association step, followed by a dissociation step in PBSF. Data were analyzed using the ForteBio Data Analysis Software 7. Kd values were calculated for antibodies with BLI responses >0.1 nm, and the data were fit to a 1:1 binding model to calculate association and dissociation rate constants. The K D values were calculated using the ratio kd/ka.

Polyreactivity Assay

Polyspecificity reagent binding was assessed as previously described (Xu et al, Protein Eng Des Sel 2013). Briefly, soluble membrane protein (SMP) and soluble cytosolic protein (SCP) fractions were prepared from Chinese hamster ovary cells and biotinylated with NHS-LC-Biotin reagent (Pierce, ThermoFisher Cat #21336). 2 million IgG-presenting yeast were transferred to a 96-well assay plate, pelleted to remove supernatant, then the pellets were resuspended in 50 uL of 1:10 diluted stock of biotinylated SCPs and SMPs and incubated on ice for 20 minutes. Cells were washed twice with ice-cold PBSF, and the samples were incubated in 50 uL of secondary labeling mix (Extravadin-R-PE, goat F(ab′) 2-anti human kappa-FITC, and propidium iodide) on ice for 20 minutes. The samples were analyzed for polyspecificity reagent binding using a FACSCanto II (BD Biosciences) with HTS sample injector. Flow cytometry data were analyzed for mean fluorescence intensity in the R-PE channel and normalized to three control antibodies exhibiting low, medium, and high MFI values.

Plasma Neutralization Assay

Infant plasma samples were tested for RSV neutralization in microtiter assays using a recombinant RSV expressing Renilla luciferase (rA2-Rluc; a gift from Dr. Michael Teng, University of South Florida [Fuentes S, Crim R L, Beeler J, Teng M N, Golding H, Khurana S. Development of a simple, rapid, sensitive, high-throughput luciferase reporter based microneutralization test for measurement of virus neutralizing antibodies following Respiratory Syncytial Virus vaccination and infection. Vaccine. 2013 Aug. 20; 31(37):3987-94.]). Hep2 cells were added to 96-well plates at a density of 1.8×104 cells per well in 100<1 of MEM with 2% FBS/1X penicillin-streptomycin solution (2% MEM) and allowed to adhere overnight at 37° C. On the day of the assay, plasma samples were serially diluted 2-fold (1:200 to 1:128,000) in 2% MEM containing rA2-Rluc and incubated for 30 min at 37° C. Culture media was aspirated from the Hep2 cells followed by the addition of 100<<per well of the plasma+rA2-Rluc mixture to duplicate wells. Cultures were maintained at 37° C. for 24 hrs and luciferase expression was quantified in cell lysates using the Renilla Luciferase Assay System (E2820, Promega, Madison, Wis.). Relative light units (RLU) were measured on a BioTek Synergy 2 microplate reader. Neutralization is expressed as the reciprocal of the highest plasma dilution to yield a 50% reduction in RLU as compared to control wells with no added plasma.

Adenoid Neutralization Assay

Adenoid tissue collected on the day of surgery was placed in a sterile 10 cm culture dish. A 1.8 cm circular disc of soft absorbent filter paper (Leukosorb #BSP0669, Pall Corporation, Port Washington N. Y.) was applied to the mucosal surface of the tissue. One ml of PBS with added protease inhibitors (Bestatin 0.1 ug/ml; Aprotinin 1 ug/ml; AEBSF 0.5 ug/ml; Leupeptin 5 ug/ml; Millipore Sigma, St. Louis Mo.) was added to directly to the tissue to moisten the disc. The tissue was allowed to stand for 30 min at room temperature. Excess PBS+ PI was then pipeted from the tissue into a 15 ml conical tube. The filter paper disc was collected with sterile forceps and placed into a separate 15 ml tube. An additional 0.5 ml of PBS+PI was added and the tube was centrifuged at 1,900×g rpm for 10 min. Supernatant recovered directly from the tissue and from the filter disc was retained and tested for RSV neutralizing activity. Supernatants were serially diluted 2-fold (1:4 to 1:256) and tested using the rA2-Rluc microtiter assay. Data is expressed as the dilution corresponding to a 50% inhibitory concentration (IC 50 ) compared to control wells with rA2-Rluc alone.

Example 3. Cluster Analysis of Neutralizing Antibodies According to Biophysical Characteristics

A set of RSV neutralizing antibodies were analysed for sequences of CDRH3 based on biophysical characteristics using a reduced alphabet scheme (Table 8).

The biophysical characteristics were classified as follows:

1 Group small amino acids with C-beta: AST

2. Backbone flexibility: G

3. Backbone rigidity: P

4. Positive charge: KR

5. Negative charge: ED

6. Medium sized polar NQH

7 Large Aromatic: FWY

8. Aliphatic: ILVMC

TABLE 8

Redcued alphabet consensus sequences of neutralizing antibodies

Difference

from

Parent in

Cluster Difference Reduced

ADI-Name Parent VH_GL VL_GL H3 H3 Number from Parent alphabet

ADI-14583 ADI-14583 VH1-18 VK2-30 AREPPVIAAGDFQH AREPPVIAAGDFQH 1 0 0

(SEQ ID NO: 1902) (SEQ ID NO: 1902)

ADI-14336 ADI-14583 VH1-18 VK2-30 AREPPVIAAGDFQH AREPPVIAAGDFQH 1 0 0

(SEQ ID NO: 1902) (SEQ ID NO: 1902)

ADI-14402 ADI-14583 VH1-18 VK2-30 AREPPVIAAGDFSH AREPPVIAAGDFSH 1 1 1

(SEQ ID NO: 1903) (SEQ ID NO: 1903)

ADI-14576 ADI-14583 VH1-18 VK2-30 ARDPPVIAAGDFQH ARDPPVIAAGDFQH 1 1 0

(SEQ ID NO: 1904) (SEQ ID NO: 1904)

ADI-14577 ADI-14583 VH1-18 VK2-30 ARGPPVIAADDFQH ARGPPVIAADDFQH 1 2 2

(SEQ ID NO: 1905) (SEQ ID NO: 1905)

ADI-14585 ADI-14583 VH1-18 VK2-30 AREPPVIAAGDFPH AREPPVIAAGDFPH 1 1 1

(SEQ ID NO: 1906) (SEQ ID NO: 1906)

ADI-20975 ADI-20975 VH1-18 VL3-21 AREQFKWNDFYFDY AREQFKWNDFYFDY 2 0 0

(SEQ ID NO: 1907) (SEQ ID NO: 1907)

ADI-19422 ADI-20975 VH3-30 VL3-21 AKEDYNWNDYYFDY AKEGYNWNDYYFDY 2 5 2

(SEQ ID NO: 1908) (SEQ ID NO: 1908)

ADI-41788 ADI-20975 VH1-8 VL3-21 ARGFYKWNDWSFDY ARGFYKWNDWSFDY 2 5 3

(SEQ ID NO: 1909) (SEQ ID NO: 1909)

ADI-41191 ADI-41191 VH1-18 VK2-30 AREPPSLSAAATLDY AREPPSLSAAATLDY 3 0 0

(SEQ ID NO: 1910) (SEQ ID NO: 1910)

ADI-19501 ADI-41191 VH1-18 VK2-30 ARDPPSEGAAGLFDY ARDPPSEGAAGLFDY 3 6 5

(SEQ ID NO: 1911) (SEQ ID NO: 1911)

ADI-20962 ADI-41191 VH1-18 VK2-30 AREPPSDTAAGTGDY AREPPSDTAAGTGDY 3 4 3

(SEQ ID NO: 1912) (SEQ ID NO: 1912)

ADI-22757 ADI-41191 VH1-18 VK2-30 ARDPPAV-AASFMDV ARDPPAV-AASFMDV 3 8 3

(SEQ ID NO: 1913) (SEQ ID NO: 1913)

ADI-41424 ADI-41191 VH1-18 VK2-30 VRDTPAIAGAATLDF VRDTPAIAGAATLDF 3 8 3

(SEQ ID NO: 1914) (SEQ ID NO: 1914)

ADI-41454 ADI-41191 VH1-18 VK2-30 AREPPSTTAAATSDY AREPPSTTAAATSDY 3 3 2

(SEQ ID NO: 1915) (SEQ ID NO: 1915)

ADI-20964 ADI-20964 VH1-18 VK2-30 ARDVPVEAATSPEF ARDVPVEAATSPEF 4 0 0

(SEQ ID NO: 1916) (SEQ ID NO: 1916)

ADI-20988 ADI-20964 VH1-18 VK2-30 ARDVPVIAAHTFEY ARDVPVIAAHTFEY 4 5 3

(SEQ ID NO: 1917) (SEQ ID NO: 1917)

ADI-21050 ADI-20964 VH1-18 VK2-30 AREMGVDAAATFDY AREMGVDAAATFDY 4 9 2

(SEQ ID NO: 1918) (SEQ ID NO: 1918)

ADI-20974 ADI-20974 VH3-21 VL1-40 ARALMATAGGLAFDI ARALMATAGGLAFDI 5 0 0

(SEQ ID NO: 1919) (SEQ ID NO: 1919)

ADI-24839 ADI-20974 VH3-21 VL1-40 ARVLVATAYGNAFDI ARVLVATAYGNAFDI 5 4 3

(SEQ ID NO: 1920) (SEQ ID NO: 1920)

ADI-41203 ADI-41203 VH5-51 VK3-15 VSLYSDYDYGALDY VSLYSDYDYGALDY 6 0 0

(SEQ ID NO: 1921) (SEQ ID NO: 1921)

ADI-36680 ADI-41203 VH5-51 VK3-15 VSLFGDYDYGALDY VSLFGDYDYGALDY 6 2 1

(SEQ ID NO: 1922) (SEQ ID NO: 1922)

ADI-36681 ADI-41203 VH5-51 VK3-15 VTLYTDYDYGAPDH VTLYTDYDYGAPDH 6 4 2

(SEQ ID NO: 1923) (SEQ ID NO: 1923)

ADI-41344 ADI-41344 VH3-21 VL1-40 ARVSSPMIRGYYLDY ARVSSPMIRGYYLDY 7 0 0

(SEQ ID NO: 1924) (SEQ ID NO: 1924)

ADI-41343 ADI-41344 VH3-21 VL1-40 ARVDTPMVRGYYFDY ARVDTPMVRGYYFDY 7 4 2

(SEQ ID NO: 1925) (SEQ ID NO: 1925)

Example 4. Exemplary Antibodies

Antibodies were assessed for RSV neutralization activity and polyreactivity. A set of antibodies with exemplary characteristics are provided in Tables 9A-C.

TABLE 9A

Antibody binding and functional characteristics

neut IC50 neut IC50 neut IC50

Neutralization - (ug/ml) (ug/ml) (ug/ml)

Antibody RSV A2 IC50 subtype A subtype B subtype A RSV PreF RSV PostF Polyreactivity

No. ADI Name (pM) (graham) (graham) (wright) Antigenic site subtype A KD subtype A KD score

Ab 2 ADI-14334 189.2 0.05 0.11 Site III 3.2E−10 N.B. 0.00

Ab 71 ADI-14405 58.3 0.04 0.04 Site IV 1.4E−10 1.2E−08 0.03

(but preF-preferring)

Ab 112 ADI-14583 124.6 0.05 0.06 Site V 4.7E−10 N.B. 0

Ab 217 ADI-20964 162.4 0.06 0.14 Site V 3.6E−10 N.B. 0

Ab 227 ADI-20974 75.4 0.003 0.09 Site III 2.9E−10 N.B. 0.11

Ab 228 ADI-20975 67 0.05 0.49 unknown 9.2E−11 1.5E−10 0.03

Ab 249 ADI-20998 74 0.03 >25 Site 0 2.6E−10 N.B. 0.11

Ab 466 ADI-36669 110.9 0.025 1.1E−09 N.B. 0.01

Ab 467 ADI-36670 141 0.008 7.5E−10 N.B. 0.01

Ab 469 ADI-36672 206.7 0.018 Likely site III 7.0E−10 N.B. 0.07

Ab 470 ADI-36674 189.8 0.014 Likely site III 7.5E−10 N.B. 0.01

Ab 832 ADI-36676 130.1 0.006 2.8E−10 N.B. 0

Ab 471 ADI-36677 144.1 0.019 5.4E−10 N.B. 0.05

Ab 516 ADI-41191 154.1 0.071 Likely site V 5.0E−10 N.B. 0.08

Ab 527 ADI-41203 23.9 0.006 4.0E−10 N.B. 0.05

Ab 532 ADI-41208 310.5 0.077 Likely site III 4.8E−10 N.B. 0.04

Ab 543 ADI-41221 65.4 0.040 3.0E−10 3.2E−10 0.01

Ab 544 ADI-41222 39.9 0.016 4.3E−10 N.B. 0.01

Ab 551 ADI-41229 228.2 0.066 1.1E−09 7.1E−10 0

Ab 554 ADI-41232 103.9 0.025 Likely site V 7.1E−10 N.B. 0.00

Ab 571 ADI-41249 51.7 0.006 3.9E−10 N.B. 0

Ab 578 ADI-41256 85.8 0.019 3.5E−10 N.B. 0.00

Ab 581 ADI-41259 122 0.015 3.4E−10 N.B. 0.00

Ab 592 ADI-41274 26.6 0.109 Likely site III 4.8E−10 N.B. 0.10

Ab 615 ADI-41302 132.9 0.006 6.5E−10 N.B. 0.03

Ab 641 ADI-41344 228.6 0.064 Likely site III 4.9E−10 N.B. 0

Ab 843 ADI-41563 139.3 0.032 6.0E−10 N.B. 0.12

Ab 868 ADI-41594 208.3 0.041 Likely site III 4.1E−10 Weak binder 0

(low response)

Ab 870 ADI-41596 179.7 0.054 3.0E−10 4.4E−10 0

TABLE 9B

Antibody VH sequence information

Anti- VH

body Germ-

No. line VH FR1 VH CDR1 VH FR2 VH CDR2 VH FR3 VH CDR3 VH FR4

Ab 2 VH3-11 EVQLVESGGGLVK VTVSSYYMT WVRQAPGKGL DISSSSTYTNYA RFTISRDNAKSSLYL ARLGITVTGVGYFDL WGRGTLV

PGGSLRLSCAASG (SEQ ID EFIS DSVKG QMNNLRAEDTAVYYC (SEQ ID NO: TVSS

(SEQ ID NO: NO: 1927) (SEQ ID (SEQ ID (SEQ ID NO: 1931) (SEQ ID

1926) NO: 1928) NO: 1929) 1930) NO: 1932)

Ab 71 VH1-18 QVQLVQSGTEVKK YTFTNYDIS WVRQAPGQGL WISGSTGNTIYA RLTMTTDTSTSTAYM ARDNVGYASGNYFDY WGQGTLV

PGASVKVSCKASG (SEQ ID EWMG QNLQG ELRSLRSDDTAIYYC (SEQ ID NO: TVSS

(SEQ ID NO: NO: 1934) (SEQ ID (SEQ ID NO: (SEQ ID NO: 1938) (SEQ ID

1933) NO: 1935) 1936) 1937) NO: 1939)

Ab 112 VH1-18 QVQLVQSGAEVKE YTFTNYGIS WVRQAPGQGL WISAYNGNIHYA RVTMTTDTSTSTGFM AREPPVIAAGDFQH WGQGTLV

PGASVKVSCKASG (SEQ ID EWLG QKVQG ELRSLRSDDTAVYYC (SEQ ID NO: TVSS

(SEQ ID NO: NO: 1941) (SEQ ID (SEQ ID NO: (SEQ ID NO: 1945) (SEQ ID

1940) NO: 1942) 1943) 1944) NO: 1946)

Ab 217 VH1-18 QVQLVQSGAEVKK YTFTHYGIS WVRQAPGQGL WISAYNGNTNYA RVTMTTDTSTSTAYM ARDVPVEAATSPEF WGQGTLV

PGASVKVSCKASG (SEQ ID EWMG QKLQG EVRSLRYDDTAVYYC (SEQ ID NO: TVSS

(SEQ ID NO: NO: 1948) (SEQ ID (SEQ ID NO: (SEQ ID NO: 1952) (SEQ ID

1947) NO: 1949) 1950) 1951) NO: 1953)

Ab 227 VH3-21 EVQLVESGGGLVK FSFSSYQIN WVRQAPGKGL SISGGSSYTDYA RFTISRDNAKKSAEL ARALMATAGGLAFDI WGQGTMV

PGGSLRLSCAASG (SEQ ID EWVS DSIKG QMKSLRADDTAVYYC (SEQ ID NO: TVSS

(SEQ ID NO: NO: 1955) (SEQ ID (SEQ ID NO: (SEQ ID NO: 1959) (SEQ ID

1954) NO: 1956) 1957) 1958) NO: 1960)

Ab 228 VH1-18 QVQLVESGTHVKK DTFNNKGIV WVRQAPGQGL WIRPNNGNTKYA RVTMTTDASTNTAYM AREQFKWNDFYFDY WGQGTLV

PGASVKVSCEASD (SEQ ID EWMG QKEQG ELRSLRSGDTAVYYC (SEQ ID NO: TVSS

(SEQ ID NO: NO: 1962) (SEQ ID (SEQ ID NO: (SEQ ID NO: 1966) (SEQ ID

1961) NO: 1963) 1964) 1965) NO: 1967)

Ab 249 VH3-33 QVQLVQSGGGVVQ FTLSTYGMH WVRQAPGKGL VIYYDESNKFYA RFTISRDDSKNTLFL ARESRPRGYSYSDFD WGQGTLV

PGRSLRLSCAASG (SEQ ID EWVA DSVQG QMNSLRAEDTAVYYC S TVSS

(SEQ ID NO: NO: 1969) (SEQ ID (SEQ ID (SEQ ID NO: (SEQ ID NO: (SEQ ID

1968) NO: 1970) NO: 1971) 1972) 1973) NO: 1974)

Ab 466 VH1-46 EVQLVQSGAEVKK YTFTTYYIH WVRQAPGQGL MINPSGGTTSYA RLTMTGDTSTSTVYM TRDFIYFYGSGDGFD WGQGTLV

PGASVRVYCKASG (SEQ ID EWMG QKFQG ELNYLRSEDTAVYYC Y TVSS

(SEQ ID NO: NO: 1976) (SEQ ID (SEQ ID (SEQ ID NO: (SEQ ID NO: (SEQ ID

1975) NO: 1977) NO: 1978) 1979) 1980) NO: 1981)

Ab 467 VH1-69 QVQLVQSGAEVKK GTFSTYTIN WVRQAPGQGL RITPSLGVPLSA RITISADKSTTTAYM ASLNYYDTTDYYLGY WGQGTLV

PGSSVKVSCKASG (SEQ ID EWMG QKFQG ELSSLGSEDTAVYYC SDS TVSS

(SEQ ID NO: NO: 1983) (SEQ ID (SEQ ID (SEQ ID NO: (SEQ ID NO: (SEQ ID

1982) NO: 1984) NO: 1985) 1986) 1987) NO: 1988)

Ab 469 VH3-11 EVQLVESGGGLVK FAFNNYYMN WVRQAPGKGL SISSASTYTDYA RFTISRDNAKNSLYL ARDYYGSGNYYNPKP WGQGTTV

PGGSLRLSCAASG (SEQ ID EWVS DSVKG HLNSLRAEDTAVYYC LDV TVSS

(SEQ ID NO: NO: 1990) (SEQ ID (SEQ ID NO: (SEQ ID NO: (SEQ ID NO: (SEQ ID

1989) NO: 1991) 1992) 1993) 1994) NO: 1995)

Ab 470 VH3-21 EVQLLESGGGLVK FKFRSYSMN WVRQAPGKGL SISSSSSYVDYA RFTISRDNAENSLYL ARAGSVPVAGTYNDY WGQGTLV

PGGSLRLSCAASG (SEQ ID EWVS GSEKG QMNSLRAEDTAMYYC (SEQ ID NO: TVSS

(SEQ ID NO: NO: 1997) (SEQ ID (SEQ ID NO: (SEQ ID NO: 2001) (SEQ ID

1996) NO: 1998) 1999) 2000) NO: 2002)

Ab 832 VH3-30 EVQLLESGGGVVQ FSFRNYDMH WVRQAPGKGL IISYDGSNK- RFTISRDTSKNTLYL ARADSSGYYKGSEYF WGQGTLV

PGRSLRLSCAASG (SEQ ID EWVA YADSVKG QMNSLRVEDTAVYYC QH TVSS

(SEQ ID NO: NO: 2004) (SEQ ID (SEQ ID NO: (SEQ ID NO: (SEQ ID NO: (SEQ ID

2003) NO: 2005) 2006) 2007) 2008) NO: 2009)

Ab 471 VH3-48 QVQLVQSGGGLVQ FTFSSYEMN WVRQAPGKGL YISSSGDTKYYA RFTVSRDNAKYSLYL ASLYDSRGYYWVFDY WGQGTLV

PGGSLRLSCAASG (SEQ ID EWIS DSVKG QMDSLRAEDTAVYYC (SEQ ID NO: TVSS

(SEQ ID NO: NO: 2011) (SEQ ID (SEQ ID NO: (SEQ ID NO: 2015) (SEQ ID

2010) NO: 2012) 2013) 2014) NO: 2016)

Ab 516 VH1-18 QVQLVQSGAEVKR YIFSHYGIS WVRQAPGQGL WISAYNGNTNYA RVTVTTDTSTSTAYM AREPPSLSAAATLDY WGQGTLV

PGASVKVSCKASG (SEQ ID EWMA QKLQG ELRSLRSDDTAVYYC (SEQ ID NO: TVSS

(SEQ ID NO: NO: 2018) (SEQ ID (SEQ ID NO: (SEQ ID NO: 2022) (SEQ ID

2017) NO: 2019) 2020) 2021) NO: 2023)

Ab 527 VH5-51 QVQLVQSGAEVRK YRFTNYWIG WVRQMPGKGL VIYPGDSDTRYS QVTMSADKSTNTAYL VSLYSDYDYGALDY WGQGTLV

PGESLKISCKASG (SEQ ID EWMG PSFQG QWSSLKASDTAIYYC (SEQ ID NO: TVSS

(SEQ ID NO: NO: 2025) (SEQ ID (SEQ ID NO: (SEQ ID NO: 2029) (SEQ ID

2024) NO: 2026) 2027) 2028) NO: 2030)

Ab 532 VH3-11 QVQLVESGGDLVK FTLSGHYMS WIRQPPGKGL SISGSSTYTNYA RFTISRDNAENSLYL ARLAYSDYGPFYFDL WGRGTLV

PGGSLRLSCAASG (SEQ ID EWVS DSVKG QMNSLRAEDTAVYYC (SEQ ID NO: TVSS

(SEQ ID NO: NO: 2032) (SEQ ID (SEQ ID NO: (SEQ ID NO: 2036) (SEQ ID

2031) NO: 2033) 2034) 2035) NO: 2037)

Ab 543 VH3-21 EVQLLESGGGLVK FTFSDYTMN WVRQAPGKGL SISITSSHIYYA RFTISRDNAKNSLYL ARELGFASSSYSYYY WGQGTTV

PGGSLRLSCAASG (SEQ ID EWVS DSVKG QINSLRAEDTAAYYC GMDV TVSS

(SEQ ID NO: NO: 2039) (SEQ ID (SEQ ID NO: (SEQ ID NO: (SEQ ID NO: (SEQ ID

2038) NO: 2040) 2041) 2042) 2043) NO: 2044)

Ab 544 VH3-30 QVTLKESGGGVVQ FNFHNYAMH WVRQAPGKGL VISYDGSNKNFA RFTISRDNSKNTLNL VRDIVRGSPLFDY WGQGTLV

PGRSQRLSCTASG (SEQ ID EWVA DSVKG QMNNLRAEDTAVYYC (SEQ ID NO: TVSS

(SEQ ID NO: NO: 2046) (SEQ ID (SEQ ID (SEQ ID NO: 2050) (SEQ ID

2045) NO: 2047) NO: 2048) 2049) NO: 2051)

Ab 551 VH3-30 QVQLVDSGGGVVQ FTFKSYGMH WVRQAPGKGL VISYDEINKYYA RFTISRDYSKNTLSL AKPKTTGYYYLDAFD WGQGTMV

PGRSLKLSCAASG (SEQ ID EWVA DSVKG QMNSLTTEDTAMYYC F TVSS

(SEQ ID NO: NO: 2053) (SEQ ID (SEQ ID NO: (SEQ ID NO: (SEQ ID NO: (SEQ ID

2052) NO: 2054) 2055) 2056) 2057) NO: 2058)

Ab 554 VH1-18 QVQLVQSGAEVKK YTFTHYGIS WVRQAPGQGL WISAYNGNTNYA RVTVTTDTSTSTAYM ARDSMGGTTLFDY WGQGTLV

PGASVKVSCKASG (SEQ ID EWMA QKLQD ELRSLRSDDTALYYC (SEQ ID NO: TVSS

(SEQ ID NO: NO: 2060) (SEQ ID (SEQ ID (SEQ ID NO: 2064) (SEQ ID

2059) NO: 2061) NO: 2062) 2063) NO: 2065)

Ab 571 VH5-51 QVQLVQSGAEVKK DTSTTYWIG WVRQMPGKGL IIFPGDSDTRYS QVTISADKSIMTAYL ATQALRGAFDI WGQGTMV

PGESLKISCQVSR (SEQ ID EWMG PSFQG QLTSLKASDTAMYYC (SEQ ID NO: TVSS

(SEQ ID NO: NO: 2067) (SEQ ID (SEQ ID NO: (SEQ ID NO: 2071) (SEQ ID

2066) NO: 2068) 2069) 2070) NO: 2072)

Ab 578 VH1-69 QVQLVQSGAEVKS GTFGSYGIS WVRQAPGQGL AIMPMFGTINYA RVTMTADESTSTVYM VRDVFYDILTGYYDA WGKGTTV

PGSSATVSCKASG (SEQ ID EWIG QKFQG DVSSLRPDDTAVYYC DYYHHYMDV TVSS

(SEQ ID NO: NO: 2074) (SEQ ID (SEQ ID NO: (SEQ ID NO: (SEQ ID NO: (SEQ ID

2073) NO: 2075) 2076) 2077) 2078) NO: 2079)

Ab 581 VH3-11 QVQLVESGGRLVK FTFSDFYMS WIRQAPGKGL YISSSGDDPNYA RFTISRDNSKNSLYL ARDEVGWNNLDYYFG WGQGTTV

PGGSLRLSCAASG (SEQ ID EWVS DSVKG QMNSLRAEDTAVYYC MDV TVSS

(SEQ ID NO: NO: 2081) (SEQ ID (SEQ ID NO: (SEQ ID NO: (SEQ ID NO: (SEQ ID

2080) NO: 2082) 2083) 2084) 2085) NO: 2086)

Ab 592 VH3-21 EVQLVESGGGLVK FSFSSYAMN WVRQAPGKGL SISAGSSYIDYA RFTISRDNAENSLFL ARVGSYTHGYEFDY WGQGTLV

PGGSLRLSCAASG (SEQ ID QWVS DSVKG QMNSLRVEDTAVYYC (SEQ ID NO: TVSS

(SEQ ID NO: NO: 2088) (SEQ ID (SEQ ID NO: (SEQ ID NO: 2092) (SEQ ID

2087) NO: 2089) 2090) 2091) NO: 2093)

Ab 615 VH3-30 QVQLVESGGGVVQ FTFSSYAMQ WVRQAPGKGL VMTNDGDDKYYA RFTISRDNSKNTLYL ARDLFEWWELLGYCY WGQGTTV

PGRSLRLSCAASG (SEQ ID EWVA DSVRG QMNNLRPEDTAVYYC AMDV TVSS

(SEQ ID NO: NO: 2095) (SEQ ID (SEQ ID NO: (SEQ ID NO: (SEQ ID NO: (SEQ ID

2094) NO: 2096) 2097) 2098) 2099) NO: 2100)

Ab 641 VH3-21 EVQLVESGGGLVK SSFSSYYMN WVRQAPGKGL SISSSSTYIDYA RFTISRDNAKNSLFL ARVSSPMIRGYYLDY WGQGTLV

PGGSLRLSCAASG (SEQ ID EWVS DSVKG QMNSLRAEDTAVYYC (SEQ ID NO: TVSS

(SEQ ID NO: NO: 2102) (SEQ ID (SEQ ID NO: (SEQ ID NO: 2106) (SEQ ID

2101) NO: 2103) 2104) 2105) NO: 2107)

Ab 843 VH4-59 QVQLYESGPGLVK DSITNNFWT WIRQPPGKGL YIYYSGSTNYNP RITNSVDLSKNQFSL ARLTSGGVDY WGQGTLV

PSETLSLTCTVSD (SEQ ID EWIG SLKS KLSSVTAADTAVYYC TVSS

(SEQ ID NO: NO: 2109) (SEQ ID (SEQ ID NO: (SEQ ID NO: (SEQ ID NO: (SEQ ID

2108) NO: 2110) 2111) 2112) 2113) NO: 2114)

Ab 868 VH3-21 EVQLVESGGGLVK FSFSSYYMN WVRQAPGKGL SISPSSSYTNYA RFTISRDNAKDSLYL ARDGLLGITIFGVVQ WGQGTLV

PGGSLRLSCAASG (SEQ ID EWVS DSVKG QMNSLRAEDTAVYYC DY TVSS

(SEQ ID NO: NO: 2116) (SEQ ID (SEQ ID NO: (SEQ ID NO: (SEQ ID NO: (SEQ ID

2115) NO: 2117) 2118) 2119) 2120) NO: 2121)

Ab 870 VH4-34 QVQLQQWGAGLLK DSFSGYFWT WIRQPPGKGL EINLSGSTNYNP RVTILVDTSKNQFSL ARGLHVSDDQDSSGY WGQGTLV

PSETLSLTCAVYG (SEQ ID EWIG SLKS KLSSVTAADTAVYYC YFHPGSFDY TVSS

(SEQ ID NO: NO: 2123) (SEQ ID (SEQ ID NO: (SEQ ID NO: (SEQ ID NO: (SEQ ID

2122) NO: 2124) 2125) 2126) 2027) NO: 2128)

TABLE 9C

Antibody VL sequence information

Anti- VL

body Germ-

No. line VL FR1 VL CDR1 VL_FR2 VL CDR2 VL FR3 VL CDR3 VL FR4

Ab 2 VL1-40 QPGLTQPPSVSGA TGSSSNIGAGY WYQQLPGTAP DNNNRPS GVPDRFSGSKSGTSASL QSYDSSLSNYV FGTGTKL

PGQRVTISC DVH KLLIN (SEQ AITGLQVEDEADYYC (SEQ ID NO: TVL

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2133) 2134) (SEQ ID

2129) 2130) 2131) 2132) NO: 2135)

Ab 71 VL3-21 SYVLTQPPSVSVA GGNNIGSKSVH WYQQRPGQAP YDSVRPS GIPERFSGSNSGNTATL QVWDSSRDHEV FGGGTKL

PGKTARIPC VLVIY (SEQ TISTVEAGDEADPYC TVL

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: (SEQ ID NO: (SEQ ID

2136) 2137) 2138) 2139) 2140) 2141) NO: 2142)

Ab 112 VK2-30 ETTLTQSPLSLPV RSSQSLVHSNG WFQQRPGQSP RVSNRDS GVPDRFSGSGSGTDFTL MQGTHWPPD FGQGTRL

TLGQPASISC NTYLS RRLIY (SEQ KISRVEAEDVGLYYC (SEQ ID NO: EIK

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2148) (SEQ ID

2143) 2144) 2145) 2146) 2147) NO: 2149)

Ab 217 VK2-30 DIVMTQTPLSLPV RSSQSLVYSDG WFQQRPGQSP KVSNRDS GVPNRFSGSGSGTDFTL VQNTHWPAYT FGQGTKV

TLGQPASISC NTYLS RRLIY (SEQ KISRVEAEDVGVYYC (SEQ ID NO: EIK

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2155) (SEQ ID

2150) 2151) 2152) 2153) 2154) NO: 2156)

Ab 227 VL1-40 QPVLTQPPSVSGA TGSGSNIGAGY WYQQVPGTAP RNTNRPS GVPDRFSGSKSGTSASL QSYDRSLSVV FGGGTKL

PGQRVTISC DVH KLLIL (SEQ AITGLQAEDEADYYC (SEQ ID NO: TVL

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2162) (SEQ ID

2157) 2158) 2159) 2160) 2161) NO: 2163)

Ab 228 VL3-21 SYELMQPPSVSVA GGSNIGSETVH WYQQKPGQAP DDTDRPS GIPERFSGSNSGNTATL QVRDSRTDDVV FGGGTKL

PGQTATITC (SEQ ID NO: VLVVH (SEQ TISGVEAGDEADFYC (SEQ ID NO: TVL

(SEQ ID NO: 2165) (SEQ ID NO: ID NO: (SEQ ID NO: 2169) (SEQ ID

2164) 2166) 2167) 2168) NO: 2170)

Ab 249 VL2-11 QPGLTQPRSVSGS TGTSSDVGTFN WYQQHPGKAP DVNQRPS GVPDRFSGSKSGNTASL CAYAGYYS FGGGTKL

PGQSVTISC YVS KLMIY (SEQ TISGLQAEDEADYYC (SEQ ID NO: TVL

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2176) (SEQ ID

2171) 2172) 2173) 2174) 2175) NO: 2177)

Ab 466 VK1-17 EICMTQSPSAMSA RASQGISNYLA WFQQKPGKVP AASSLQS GVPSRFSGSGSGTEFTL LQHNSYPFT FGPGTKV

SVGDRVTITC (SEQ ID NO: KRLIY (SEQ TITSLQPEDFATYYC (SEQ ID NO: EIK

(SEQ ID NO: 2179) (SEQ ID NO: ID NO: (SEQ ID NO: 2183) (SEQ ID

2178) 2180) 2181) 2182) NO: 2184)

Ab 467 VK3-15 DIVLTQTPATLSV RASHSVSNNLA WYQQKPGQAP SASTRAT GIPARFSGRGSGTEFTL QQYNNWPPEYT FGQGTKV

SPGERATLSC (SEQ ID NO: RLLIY (SEQ TISSLQPEDFAVYYC (SEQ ID NO: DIK

(SEQ ID NO: 2186) (SEQ ID NO: ID NO: (SEQ ID NO: 2190) (SEQ ID

2185) 2187) 2188) 2189) NO: 2191)

Ab 469 VL1-40 QPVLTQPPSVSGA TGSSSNIGAGY WYRQFPGTAP GNTNRPS GVPDRFSGSKSGTSASL QSYDSSLKGV FGGGTKL

PGQRVTISC DVH ELLIY (SEQ AITGLQAEDEADYYC (SEQ ID NO: TVL

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2197) (SEQ ID

2192) 2193) 2194) 2195) 2196) NO: 2198)

Ab 470 VL1-40 QSVLTQPPSVSGA TGSSSNIGAGY WYQHLPGTAP GNNNRPA GVPDRFSGSKSGTSASL QSYDRSLSVL FGGGTKV

PGQRVTISC DVH KLLIH (SEQ VITGLQADDEADYYC (SEQ ID NO: TVL

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2204) (SEQ ID

2199) 2200) 2201) 2202) 2203) NO: 2205)

Ab 832 VL3-21 SYELTQLPSVSVA GGNNIGTKSVQ WYQHKPGQAP DDSDRPS DIPERFSGSNSGNTATL QVWDSSSDHYV FGTGTKL

PGQTARITC (SEQ ID NO: VLVVY (SEQ TISRVEAGDEADYYC (SEQ ID NO: TVL

(SEQ ID NO: 2207) (SEQ ID NO: ID NO: (SEQ ID NO: 2211) (SEQ ID

2206) 2208) 2209) 2210) NO: 2212)

Ab 471 VK1-33 DIVMTQSPSSLSA QASQDISTYLN WYQHKPGKAP DASNLEP GVPSRFSGSGSGTDFTF LQHDNLPPT FGQGTKV

SVGDRVTITC (SEQ ID NO: NLLIY (SEQ TISSLQPEDIATYYC (SEQ ID NO: DIK

(SEQ ID NO: 2214) (SEQ ID NO: ID NO: (SEQ ID NO: 2218) (SEQ ID

2213) 2215) 2216) 2217) NO: 2219)

Ab 516 VK2-30 EIVMTQSPLSLPV RSNQSLVYSDG WFQQRPGQSP KVSNRDS GVPDRFSGSGSGTDFTL MQVTHWPHE FGQGTKL

TLGQPASISC NIYLS RRLIY (SEQ KISRVEAEDVAVYYC (SEQ ID NO: EIK

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2225) (SEQ ID

2220) 2221) 2222) 2223) 2224) NO: 2226)

Ab 527 VK3-15 EIVMTQSPATLSV RASENVGRNLA WYQQKPGQAP GASIRAT GILARFSGSGSGTEYTL QQYHDWPSFT FGPGTKV

SPGERATLSC RLLIY (SEQ TISSLQSEDFAVYYC (SEQ ID NO: DIK

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2232) (SEQ ID

2227) 2228) 2229) 2230) 2231) NO: 2233)

Ab 532 VL1-40 QSVLTQPPSVSGA TGSSSNIGAGY WYQQLTGTAP DNNNRPS GVPDRFSGSKSGTSASL QSYDSRLSAPYV FGTGTKL

PGQRVTISC DVH KLLIF (SEQ AITGLQAEDEADYYC (SEQ ID NO: TVL

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2239) (SEQ ID

2234) 2235) 2236) 2237) 2238) NO: 2240)

Ab 543 VL2-11 QSALTQPRSVSGS TGTSSDVGDYN WYQQHPGTAP DVTQRPS GVPDRFSGSKSANTASL CCSFAGNYV FGTGTKV

PGQSVTISC SVS KLIIF (SEQ TISGLQPEDEADYY- (SEQ ID NO: TVL

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2246) (SEQ ID

2241) 2242) 2243) 2244) 2245) NO: 2247)

Ab 544 VL3-21 QPVLTQPPSLSVA GGNNIGSKIVH WYQQKPGQAP DDDDRPS GIPERFSGSNSGNTATL QVWDRSSDNYV FGTGTKV

PGQTAWITC VVVVY (SEQ TIRRVEVGDEADYYC (SEQ ID NO: SVL

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2253) (SEQ ID

2248) 2249) 2250) 2251) 2252) NO: 2254)

Ab 551 VK1-33 ETTLTQSPSSLSA QASQDISNYLN WYQQKPGKAP DASNLET GVPSRFSGSGSGTDFTF QQHDNVPPT FGQGTKV

SVGDRVTITC KLLIY (SEQ TISSLQSEDIATYYC (SEQ ID NO: DIK

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2260) (SEQ ID

2255) 2256) 2257) 2258) 2259) NO: 2261)

Ab 554 VK2-30 DIVLTQTPLSLPV RSSQSLVYSDG WFQQRPGQSP KVSNRDS GVPDRFTGSGSGTDFTL MQGTHWPPMYT FGQGTKL

TLGQPASISC NTYLN RRLIY (SEQ KISRVEAEDVGVYYC (SEQ ID NO: EIK

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2267) (SEQ ID

2262) 2263) 2264) 2265) 2266) NO: 2268)

Ab 571 VK1-33 DIRLTQSPSSLSA QASQDISNYLN WYQQKPGKAP DASYLET GVPSRFSGSGSGTDFTF QQYDDLLFT FGPGTKL

SVGDRVTITC KLLIY (SEQ TISSLQPEDFATYYC (SEQ ID NO: EIK

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2274) (SEQ ID

2269) 2270) 2271) 2272) 2273) NO: 2275)

Ab 578 VK2-30 DIVMTQSPLSLPV RSGQSLVHSDG WFQQRPGQSP KVSNRGS GVPDRFSGSGSGTDFTL MQGTHWPRT FGQGTKV

TLGQPASISC NTYLN RRLIY (SEQ KISRVEAEDVGVYFC (SEQ ID NO: DIK

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 22281) (SEQ ID

2276) 2277) 2278) 2279) 2280) NO: 2282)

Ab 581 VK2-30 DIVMTQSPLSLPV RSSQSLVHSDG WFHQRPGQSP KVSNRDS GVPNRFSGGGSGTDFTL MQGTHWQKT FGQGTKV

TLGQPASISC NTYLS RRLIY (SEQ KISRVEAEDVGFFYC (SEQ ID NO: EIK

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2288) (SEQ ID

2283) 2284) 2285) 2286) 2287) NO: 2289)

Ab 592 VL1-40 QPVLTQPPSVSGA TGSNSNIGAGY WYQQLPGTAP ASTIRPS GVPDRFSGSKSGTSASL QSYDRNLSVV FGGGTKV

PGQRVTISC DVH KLLIY (SEQ AITGLQAEDEADYYC (SEQ ID NO: TVL

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2295) (SEQ ID

2290) 2291) 2292) 2293) 2294) NO: 2296)

Ab 615 VL2-8 QSVLTQPPSASGS TGTSSDVGAYN WYQQHPGKAP EVYKRPS GVPDRFFGSKSGNTASL SSYAGSNTLGV FGGGTKV

PGQSVTISC YVS KLIIY (SEQ TVSGLQAEDEADYYC (SEQ ID NO: TVL

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2302) (SEQ ID

2297) 2298) 2299) 2300) 2301) NO: 2303)

Ab 641 VL1-40 QPVLTQPPSVSGA TGSSSNIGAGY WYQQLPGTAP GNSNRPS GVPDRFSGSKSGTSASL QSYDSSLSGSV FGGGTKL

PGQRVTISC DVH KLVIH (SEQ AITGLQDEDEADYYC (SEQ ID NO: TVL

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2309) (SEQ ID

2304) 2305) 2306) 2307) 2308) NO: 2310)

Ab 843 VL1-40 QSVLTQPPSLSGA TGSSSNIGADY WYQQLPGTAP QNTNRPS GVPDRFSASKSGTSVSL QSYDSSLSAWV FGGGTKL

PGQRVTISC HVH KLLIY (SEQ AITGLQAEDEADYYC (SEQ ID NO: TVL

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2316) (SEQ ID

2311) 2312) 2313) 2314) 2315) NO: 2317)

Ab 868 VL1-40 QSVVTQPPSVSGA TGSSSNIGAGY WYQQLPGTAP GNTNRPS GVPDRFSASKSGTSASL QSYDSSLSVV FGGGTKL

PGQRVTISC DVH KLLIY (SEQ AITGLQAEDEADYYC (SEQ ID NO: TVL

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2323) (SEQ ID

2318) 2319) 2320) 2321) 2322) NO: 2324)

Ab 870 VK4-1 DIRMTQSPDSLAV KSSQSVLYSSN WYQQKPGQPP WASTRES GVPDRFSGSGSGTDFTL QQYYSTPLT FGGGTKV

SLGERATINC NKNYLA KLLIN (SEQ AISSLQAEDVAVYYC (SEQ ID NO: EIK

(SEQ ID NO: (SEQ ID NO: (SEQ ID NO: ID NO: (SEQ ID NO: 2330) (SEQ ID

2325) 2326) 2327) 2328) 2329) NO: 2331)

An informal sequence listing is provided below in Table 5.

TABLE 5

Informal Sequence Listing

Antibody SEQ ID

No. NO: Sequence Clone # (ADI) Descriptors

Ab 1 1 EVQLVETGGGLVKPGGSLRLSCADSG FPFSSYSMH WVRQAPGKGLEWVA SISSSSS ADI-14333 Heavy chain variable region

FINYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYFC AREAACGGDCYGYYFD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 1 2 QSVVTQPPSASGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKVLIS GNSNR ADI-14333 Light chain variable region

PS GVPARFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV EGGGTQLTVL (“LC”) amino acid sequence

Ab 2 3 EVQLVESGGGLVKPGGSLRLSCAASG VTVSSYYMT WVRQAPGKGLEFIS DISSSSTY ADI-14334 Heavy chain variable region

TNYADSVKG RFTISRDNAKSSLYLQMNNLRAEDTAVYYC ARLGITVTGVGYFDL WG (“HC”) amino acid sequence

RGTLVTVSS

Ab 2 4 QPGLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIH DNNN ADI-14334 Light chain variable region

RPS GVPDRFSGSKSGTSASLAITGLQVEDEADYYC QSYDSSLSNYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 3 5 EVQLVESGGGLVQPGRSLRLSCTASG FTFGDYAMS WVRQAPGKGLEWVG FIRSN ADI-14335 Heavy chain variable region

AFGGTSEYAASVKG RFTISRDDSKSIAYLQMNSLKTEDTAVYYC TRDGIHDYGDSYY (“HC”) amino acid sequence

YYGMDV WGQGTTVTVSS

Ab 3 6 DIQLTQSPSSLSASVGDRVTITC RASQTVTTYLN WYQQKPGKAPKLLIY GASSLQS G ADI-14335 Light chain variable region

VPSRFSGSGSGTDFTLTINSLQPEDFATYYC QQTYSTVTF GPGTKVEIK (“LC”) amino acid sequence

Ab 4 7 EVQLLESGGEVKKPGASVKVSCKASG YTFTNYGIS WVRQAPGQGLEWMG WISAY ADI-14336 Heavy chain variable region

NGNTNYAQKLQG RVTMTTDTSTSTAYMEVRRLRSDDTAVYYC AREPPVIAAGDFQ (“HC”) amino acid sequence

H WGQGTLVTVSS

Ab 4 8 DIVMTQTPLSLPVTLGQPASISC RSSQSLVHSDTNIYLS WFQQRPGQSPRRLIY KVSN ADI-14336 Light chain variable region

RDS GVPDRFSGSGSGTDFTLRISRVEAEDVGVYYC MQGTHWPPD FGQGTRLEIK (“LC”) amino acid sequence

Ab 5 9 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-14337 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREYYDSSGYTNWFDP (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 5 10 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-14337 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLAWV EGGGTQLTVL (“LC”) amino acid sequence

Ab 6 11 EVQLVESGGGVVQPGRPLRLSCAASG FTFSTYDLY WVRQAPGKGLDWVA IISPDG ADI-14338 Heavy chain variable region

NKKYYADSVKG RFTISRDNSKNTLFLHMNSLRAEDTAVYYC ARDYGNYFGSGSYYR (“HC”) amino acid sequence

YFDL WGRGTLVTVSS

Ab 6 12 DIQLTQSPSSLSASVGDRVTITC RASQSISSHLN WYQQKPGKAPKLLIY ASSSLQS GV ADI-14338 Light chain variable region

PSRFSGSGSGTDFTLTISGLQPEDFATYYC QQSYSTPFT FGPGTKVEIK (“LC”) amino acid sequence

Ab 7 13 QVQLVESGGGVLQPGRSLRLPCEASG FTFNKYAMH WVRQAPGKGLEWVA AVSY ADI-14339 Heavy chain variable region

DGGNKFYAESVKG RFTISRDNSKNTLYLQMNSLKPEDTAVYYC ARDRWELLHGLDY (“HC”) amino acid sequence

WGLGTLVTVSS

Ab 7 14 SYELTQPPSVSVSPGQTARITC SGEALAKQYAY WYQQKPGQAPVLVIY KDNERPS GI ADI-14339 Light chain variable region

SERFSGSSSGTTVTLTISGVQAEDEADYYC QSADSSGTYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 8 15 EVQLVESGGGLVKPGGSLRLSCAASG FTLSSYTMN WVRQAPGRGLEWVS SIYSTSS ADI-14340 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDSQAVTGTDLYFDS (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 8 16 QPGLTQPPSVSVAPGKTARITC GGNNIGRKNVH WYQQKPGQAPILVIY YDSDRPS ADI-14340 Light chain variable region

GIPERFSGSNSGNTATLTISRVEDGDEADYYC QVWDSSNDHVI FGGGTQLTVL (“LC”) amino acid sequence

Ab 9 17 QVQLVQSGGGLVQPGGSLRLSCAGSG FTFSDYEMN WVRQAPGKGLEWLS YISSS ADI-14341 Heavy chain variable region

GSIIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTGLYYC ARANHRHYYGMDV (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 9 18 DIRLTQSPSTLSASVGDRVTITC RASQSIGSWLA WYQQKPGKAPKLLIY KASSLES GV ADI-14341 Light chain variable region

PSRFSGSGSGTEFTLTISSLQPDDFATYYC QQYNSYSYT FGRGTRLEIK (“LC”) amino acid sequence

Ab 10 19 QVTLKESGPVLVKPTETLTLTCTVSG FSLSNAKMGVS WIRQPPGKALEWLA YISSND ADI-14342 Heavy chain variable region

EKSYSTSLKS RLTISKDTSKSQVVLTMTNMDPVDTATYYC ARILLYDSSGYYLWYFDL (“HC”) amino acid sequence

WGRGTLVTVSS

Ab 10 20 DIQVTQSPSSLSASVGDRVTITC RASQRITSYLN WYQHKPGKAPKLLIF AASSLHS GV ADI-14342 Light chain variable region

PSTFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 11 21 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYGVN WVRQAPGQGLEWMG RIIP ADI-14343 Heavy chain variable region

MFGTSNYAQKFQG RVTITADGSTSTAYMELSSLRSEDTAVYYC ARVGSPTTGAIMG (“HC”) amino acid sequence

V WGQGTTVTVSS

Ab 11 22 DIVLTQTPLSLPVTPGEPASISC RSSQSLLQSNGFNYLD WYLQKPGQSPKLLIY MGSN ADI-14343 Light chain variable region

RAS GVPDRFSGSGSGTDFTLIISRVEAEDVGVYYC MQAIESPLT FGGGTKVDIK (“LC”) amino acid sequence

Ab 12 23 QVQLVQSGGGLVQPGGSLRLSCAASG FTFRTYALS WVRQAPGKGLEWVS SILGSG ADI-14344 Heavy chain variable region

GSTYYADSVKG RFTISRDNSKNTLYLQLNSLRAEDTAVYFC AKLAVAGLLHHYYGLD (“HC”) amino acid sequence

V WGQGTTVTVSS

Ab 12 24 SYELTQPPSVSVSPGQTASITC SGDKLENKYAC WYQQKPGQSPVLLIY QDTKRPS GI ADI-14344 Light chain variable region

PERFSGSNSGTTATLTISGTQALDEADYYC QAWDSSTASVL FGGGTQLTVL (“LC”) amino acid sequence

Ab 13 25 QITLKESGAEVKKPGASVKVSCKVSG YTLSDFSMH WVRQAPGKGLEWMG SFDPE ADI-14345 Heavy chain variable region

DGETVDAQKFQG RVTMTEDRSTATAYMELRSLRSEDTAVYYC GTPASAGQVDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 13 26 DIVLTQSPSSLSASVGDRVTITC RASQSISSYLH WYQQKPGKAPKLLIY AASSLQS GVP ADI-14345 Light chain variable region

SRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYITPYT FGQGTKLEIK (“LC”) amino acid sequence

Ab 14 27 EVQLLESGGGLVKPGGSLRLSCAASG FRFSSYSMN WVRQAPGKWLEWVS SISASSS ADI-14346 Heavy chain variable region

YTDYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREDYLSSGSLLHWFD (“HC”) amino acid sequence

P WGQGTLVTVSS

Ab 14 28 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNNNR ADI-14346 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSRLSVL FGGGTKVTVL (“LC”) amino acid sequence

Ab 15 29 EVQLVESGGGLVKPGGSLRLSCAASG FTFRDYYMN WIRQAPGKGLEWVS DISASSS ADI-14347 Heavy chain variable region

YTNYADSVKG RFTISRDNAKTSLYLQMNSLRAEDTAVYYC AREVVTAMGGYYFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 15 30 QSVVTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIY GNNN ADI-14347 Light chain variable region

RPS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSGV FGTGTKVTVL (“LC”) amino acid sequence

Ab 16 31 QVQLVESGGGVAQPGGSLRLSCVASG FTFSNYGMH WVRQAPGKGLEWVA FIRSD ADI-14348 Heavy chain variable region

GSKKYYGDSGKG RFTISRDNSKNTLYLQMNSLRAEDTALYYC ARERAGATFAFDI W (“HC”) amino acid sequence

GQGTTVTVSS

Ab 16 32 QSALTQPRSVSGSPGQSVTISCTG TSSDVGGYNFVS WYQHHPGKAPKLMIY DVTN ADI-14348 Light chain variable region

RPS GVPDRFSGSKSGNTASLTISGLQADDEADYYC CSYAGGFTFYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 17 33 EVQLVESGAEVKKPGSSVKVSCKASG GTLSSYAFS WVRQAPGQGLEWMG GVIPIS ADI-14349 Heavy chain variable region

ATSDYAQKFQG RVTITADESTSTVYMELRSLRSEDTAVYYC ARDTRYSSGWFYDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 17 34 DIRLTQSPDSLAVSLGERATINC KSSQSVLYSSNNKNYLA WYQQKPGQPPNLLIY WA ADI-14349 Light chain variable region

STRDS GVPDRFSGSGSGTDFTLTISRLQAEDVAVYYC QQYYSTPYT FGQGTKLEIK (“LC”) amino acid sequence

Ab 18 35 EVQLVESGPGLVKPSETLSLTCTVSG DSVSNNNYYWN WIRQSPGKGLEWIG YIYYS ADI-14350 Heavy chain variable region

GSTDYNPSLKS RVTISVDTSKNQFSLNLRSVTAADTAIYFC ASAPWGMFTILGVVPSY (“HC”) amino acid sequence

YYGMDV WGQGTTVTVSS

Ab 18 36 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GSSNR ADI-14350 Light chain variable region

PS GVPDRFSGSRSGTSASLAITGLQAEDEADYYC QSYDGSLGVYV FATGTKVTVL (“LC”) amino acid sequence

Ab 19 37 EVQLLESGGGLVQPGGSLRLSCSASG FTFSTYWMH WVRQAPGKGLVWVS RINGD ADI-14351 Heavy chain variable region

GNDRNYADSVKG RFTISRDNAKNTVYLQMNSLRAEDTAVYYC ARGGATGDFYFG (“HC”) amino acid sequence

MDV WGQGTTVTVSS

Ab 19 38 SYELTQPPSVSVAPGKTAKITC GGNNIGTKSVH WYQQKPGQAPVLVIY YDTDRPS GI ADI-14351 Light chain variable region

PERFSGSNSGNTATLTISRVEAGDEADYYC QVWDSSNSDHVGV FGGGTQLTVL (“LC”) amino acid sequence

Ab 20 39 EVQLLETGPGLVKPSQTLSLICAVSG GSISSGGYSWS WIRQPPGKGLEWVG YISYSG ADI-14352 Heavy chain variable region

STYYNPSLKS RVTISVDTSKNQFSLKLNSVTAADTAVYFC ARVDGIYSSGMRFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 20 40 DIQLTQSPGTLSLSPGERATLSC RASQSVSSYYLA WYQQKPGQAPRLLIY GTSSRAT G ADI-14352 Light chain variable region

IPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGRSPL FGQGTRLEIK (“LC”) amino acid sequence

Ab 21 41 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYTIS WVRQAPGQGLEWMG RIKPIIG ADI-14353 Heavy chain variable region

IANNAQRFKG RVTITAEKSTGTAYMELSSLTSEDTAVYYC ARGGYDYYGMDV WGQ (“HC”) amino acid sequence

GTTVTVSS

Ab 21 42 QSALTQPASVSGSPGQSITISC TGTSSDVGGYNYVS WHQQHPGKAPKLLIY DVSNR ADI-14353 Light chain variable region

PS GVSNRFSGSKSGNTASLSISGLQAEDEADYYC SSFTSTSTPYV FGTGTQLTVL (“LC”) amino acid sequence

Ab 22 43 QVQLVQSGAEVKKPGSSAKVSCKASG GTFSSYTIS WVRQAPGQGLEWMG RIIPFL ADI-14354 Heavy chain variable region

GIANYAQKFQG RVTFTADKSTSTVYMDLSRLRSEDTALYYC AREPMYYGGDSYAFD (“HC”) amino acid sequence

V WGQGTTVTVSS

Ab 22 44 QSVLTQPASMSGSPGHSITISC TGTSSDVGAYNYVS WYQQHPGKAPKLMIY DVSN ADI-14354 Light chain variable region

RPS GVSSRFSGSKSGNTASLTISGLQPEDEADYYC SSFTTSSTRV EGTGTKLTVL (“LC”) amino acid sequence

Ab 23 45 EVQLVESGPTLVKPTQTLTLICTFSG FSLSTSGVGVG WIRQPPGKALEWLA VIYWD ADI-14355 Heavy chain variable region

DDKTYSPSLKS RLTITKDTSKNQVVLTMTNMNPVDTATYYC ARCPAPVYSYGVDV (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 23 46 QSALTQPASVSGSPGQSITISC TATSSDFGGYDYVS WYQQHPGEAPKLMIS DVTNR ADI-14355 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSYTTPYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 24 47 QVQLQESGAGLLKPSETLSLTCAVYG GSFSGYYWS WIRQPPGKGLEWIG EINHSGS ADI-14356 Heavy chain variable region

TNYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARDQRIVVVGAATEPYYYY (“HC”) amino acid sequence

YGMDV WGQGTTVTVSS

Ab 24 48 QPVLTQPPSVSVSPGQTARITC SGDALPKQYAY WYQQKPGQAPVLVIY KDSERPS G ADI-14356 Light chain variable region

IPERFSGSSSGTTVTLTISGVQAEDEADYYC QSADSSGTYRV FGGGTKLTVL (“LC”) amino acid sequence

Ab 25 49 EVQLVESGGGVVQPGRSLRLSCAASG FTFSNYAMH WVRQAPGKGLEWVS IISYDG ADI-14357 Heavy chain variable region

SNKYYADSVKG RFTISRDNSKNTLYLQINSLRTEDTAVYYC ARARKRIPIVVVTAPYYY (“HC”) amino acid sequence

GMDV WGQGTTVTVSS

Ab 25 50 DIRVTQSPSSLSASVGDRVTITC RASQSISSYLH WYQQQPGKAPNLLIY AASNLQS G ADI-14357 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYTTPHT FGQGTKVEIK (“LC”) amino acid sequence

Ab 26 51 QVQLVQSGGGLVKPGGSLRLSCVASG FTFSDYYMT WIRQAPGKGLEWVS YISGSS ADI-14358 Heavy chain variable region

AYTIYADSVKG RFTISRDNAKNSLYLQMNGLRAEDTAVYYC ARVSWVRSLDS WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 26 52 QSALTQPASVSGSPGQSITISC TGSTSDVGLYNYVS WYQLHPGKAPKLIIY DVRHRPS ADI-14358 Light chain variable region

GVSDRFSASKSGNTASLTISGLQAEDEADYYC CSYTSSSTYV FGSGTQLTVL (“LC”) amino acid sequence

Ab 27 53 QVQLVQSGPALVKPTQTLTLICTFSG FSLSTSGMCVS WIRQPPGKALEWLA RIDW ADI-14359 Heavy chain variable region

DDDKYYSTSLKT RLTISKDTSKNQVVLTMTNMDPVDTATYYC ARATNYDSSGYYSLY (“HC”) amino acid sequence

FDY WGQGTLVTVSS

Ab 27 54 DIQMTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIY AASSLQS G ADI-14359 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 28 55 QVQLVQSGAEVKKPGASVKVSCKASG YTFTTYSMH WVRQAPGQRLEWMG WIN ADI-14360 Heavy chain variable region

AGNGNTKYSQKFQG RVTITRDTSASTAYMELSSLRSEDTAVYYC ARDGVGGAYYYG (“HC”) amino acid sequence

EMDV WGQGTTVTVSS

Ab 28 56 EIVLTQSPLSLPVTPGEPASISC RSSQSLLHSNGYNYLD WYLQKPGQSPQLLIYL GSNR ADI-14360 Light chain variable region

AS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPRFT FGPGTKVEIK (“LC”) amino acid sequence

Ab 29 57 EVQLLESGGGFVQPGGSLRLSCAASG FTFSSYAVN WVRQAPGKGLEWVS LISGSGR ADI-14361 Heavy chain variable region

TDYTDSVKG RFTISRDNAKNTLFLQMNSLRVEDTAVYYC AKSWGSSGYGYLDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 29 58 QSGLTQPPSVSGAPGQRVTISC TGSSSNIGPGTDVH WYQHFPGTAPKLLIF GNSNR ADI-14361 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEAYYYC QSYDRILSASV FGGGTKLTVL (“LC”) amino acid sequence

Ab 30 59 EVQLLESGGGLVQPGGSLRLSCAASG FTFSSYAMS WVRQAPGKGLEWVS GISGSG ADI-14362 Heavy chain variable region

GSTYYADSVKG RFTISRDNSKNTLYLEMNSLRAEDTAVYYC AKRYYYGSGTYTFDI W (“HC”) amino acid sequence

GQGTMVTVSS

Ab 30 60 DIRLTQSPSSLSASVGDRVTITC RASQSIISYLN WYQQKPGKAPKLLIY AASSLQS GVP ADI-14362 Light chain variable region

SRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 31 61 QVQLVESGGGLVKPGGSLRLSCAASG FTFSDYYMS WIRQAPGKGLEWVS YISGGG ADI-14363 Heavy chain variable region

TYTKYADSVKG RFTISRDNAKNSVYLQMNSLRAEDTAVYYC ARDVALVGWELRYG (“HC”) amino acid sequence

MDV WGQGTTVTVSS

Ab 31 62 ETTLTQSPGTLSLSPGERATLSC RARENVNSSYLA WYQQKPGQAPRLLIY GASSRAT ADI-14363 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYAISPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 32 63 QVQLVQSGAEVKKPGESLKISCKGSG YSFTSHWIG WVRQMPGKGLEWMG ITDPG ADI-14364 Heavy chain variable region

DSDTRYSPSFQG QVTISADKSISTAYLQWSSLKASDTAMYYC AREPRRWMTTETNG (“HC”) amino acid sequence

PYYFDN WGQGTLVTVSS

Ab 32 64 SYVLTQPPSVSVAPGKTARITC GGNNIGSKSVH WYQQKPGQAPVLVIY YDSDRPS GI ADI-14364 Light chain variable region

PERFSGSNSGNTATLTISRVEAGDEADYYC QVWDSSSDNRV FGGGTKVTVL (“LC”) amino acid sequence

Ab 33 65 QVQLVQSGAEVKKPGASVKVSCKVSG YTLTKLSMH WVRQAPGKGLEWMG FFDP ADI-14365 Heavy chain variable region

EDGDTLYAQKFQG RVTMTEDTSSDTPYMELRSLRSEDTAVYYC ASPAAAGQFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 33 66 DIVMTQSPSSLSASVGDRVTITC RASQFISSYLH WYQQKTGKAPKLLIY AASSLQS GV ADI-14365 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYNTPRT FGQGTKLEIK (“LC”) amino acid sequence

Ab 34 67 QVQLVQSGTEVKKPGASVKVSCKASG YTFNMYGVS WVRQAPGQGLEWMG WIS ADI-14366 Heavy chain variable region

AYNGNTNYAQKFQG RVTMTIDTSTTTAYMELRSLRSDDTAMYYC ARDFQAEEPLS (“HC”) amino acid sequence

NWFDP WGQGTLVTVSS

Ab 34 68 DIVMTQTPSSLSASVGDRVIITC RASQSISRYIN WYQKKPGKAPKFLIY AVSSLGS GVP ADI-14366 Light chain variable region

SRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPFT FGPGTKVDIK (“LC”) amino acid sequence

Ab 35 69 EVQLLESGGGLVQPGGSLRLSCAASG FTFGSYDMN WVRQAPGKGLEWVS GISGS ADI-14367 Heavy chain variable region

GDATYYADSVKG RFTISRDNSKNMLYLQMNSLSAEDMAVYYC ARDRAFTMKYNS (“HC”) amino acid sequence

NWYKIY WGQGTMVTVSS

Ab 35 70 EIVLTQSPGTLSLSPGERATLSC RASQSVTSSYLA WYQQKPGQAPRLLIY GAFSRAT G ADI-14367 Light chain variable region

IPDRFSGSGSGTDFTLTISRLEPEDFAVYYC HHYGTSRWT FGQGTKVDIK (“LC”) amino acid sequence

Ab 36 71 EVQLVESGGGLVKPGGSLRLSCAASG FTFINAWMS WVRQAPGKGLEWVG RIKSK ADI-14368 Heavy chain variable region

ADGGTTDDAAPVKG RFTISRDDSKNTLYLQMNSLKIEDTAVYYC ATDVLPLYNWNL (“HC”) amino acid sequence

GWNFDL WGRGTLVTVSS

Ab 36 72 SYVLTQPPSVSVAPGKTARITC GGNNIADKSVH WYQQKPGQAPVLVMY YDTDRPS ADI-14368 Light chain variable region

GIPERFSGFNSGNTATLTISRVEAGDEADYYC QVWDSSSDHVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 37 73 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSNAIS WVRQAPGQGLEWMG GIIPIF ADI-14369 Heavy chain variable region

ATANYAQNFQD RVTITADESTGTAYMELSSLRYEDTAVYYC AKSAIHSGYHGPARS (“HC”) amino acid sequence

GFYQNGMDV WGQGTTVTVSS

Ab 37 74 SYELTQPPSASGTPGQRVTISC SGSSSNIGINPVN WYQHFPGTAPKLLIY RNNQRPS ADI-14369 Light chain variable region

GVPDRFSGSKSGTSASLAISGLQSEDEAVYYC AAWDDRLNGPV FGGGTQLTVL (“LC”) amino acid sequence

Ab 38 75 EVQLVESGGGVVQPGKSLRLSCAASG FSFSTFAMH WVRQAPGKGLEWVA VISYD ADI-14370 Heavy chain variable region

GSNKFYADSVKG RFTISRDSSKNTLYLQMNSLRAEDTAVYYC ARGGYSSGWYVTHF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 38 76 QSVLTQPPSASGSPGQSVTISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY EVSKR ADI-14370 Light chain variable region

PS GVPDRFSGSKSGNTASLIVSGLQAEDEADYYC SSYAGSNNLYV EGTGTKLTVL (“LC”) amino acid sequence

Ab 39 77 EVQLVESGGGLVQPGGSLRLSCAASG FTFSNYAMT WVRQAPGKGLEWLS SISGSG ADI-14371 Heavy chain variable region

GSTYYADSVKG RFTISRDNSRNTLYVQMNSLRVEDTAFYYC AKAFYEYGAGSPGDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 39 78 DIQLTQSPSSLSASVGDRVTITC RASQSIGTNLN WYQQKPGKAPKFLIY AASSLQR G ADI-14371 Light chain variable region

VPSRFSGSGSGSEFTLTISSLQPEDFATYYC QQSYSTLPIT FGQGTKLEIK (“LC”) amino acid sequence

Ab 40 79 QVQLLESGGGLVQPGGSLRLSCAASG FTFSNYAMG WVRQAPGQGLEWVS RISAT ADI-14372 Heavy chain variable region

GGSTHYADSVRG RFTISRDNSKNTLYLQMNSLKAEDTAVYYC AKDRGYSRNLTPDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 40 80 ETTLTQSPSSLSASVGDRVTITC RASQGITNDLG WYQKKPGKAPKLLIY VASSLQS GV ADI-14372 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC LQDYNYPIT FGQGTKVDIK (“LC”) amino acid sequence

Ab 41 81 QVQLQQWGAGLLKPSETLSLTCAVYG GSFSGSYWS WIRQPPGKGLEWIG EINHSG ADI-14373 Heavy chain variable region

STSYNPSLKS RVTISVDTSKKQFSLKLSSMTAADTAVYYC AGGFYYDSSGSYAPHPTF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 41 82 DIVMTQTPATLSVSPGERATLSC RASQSVSSNLA WYQQKPGQAPRLLIY GASTRAT ADI-14373 Light chain variable region

GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPRT FGQGTKVEIK (“LC”) amino acid sequence

Ab 42 83 QVQLVQSGGVVVQPGGSLRLSCAASG FNFDDFTMH WVRQAPGKGLEWVS LITW ADI-14374 Heavy chain variable region

DGGITYYADSVKG RFTISRDNGKNSLYLRMNSLRTEDTALYYC AKDGDRYSGYAFLD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 42 84 SYELTQPPSVSVAPGKTARLTC GGNNIGSESVH WYQQRPGQAPVLVSY YNGDRPS ADI-14374 Light chain variable region

GIAERISASKSGNTATLTIYRVEAGDEADYYC QVWHSSSDHFV FGTGTQLTVL (“LC”) amino acid sequence

Ab 43 85 EVQLVESGGGLVQPGGSLRLSCAVSG FTFSNYAVS WVRQAPGKGLEWVS GISGSG ADI-14375 Heavy chain variable region

GTTYYVDSVKG RFTVSRDNSKNTLFLQLNSLKAEDTAVYYC AKDWGYSGGRPYFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 43 86 QSVLTQPPSVSGAPGQRVTISC TASSSNIGPIYDVH WYQQLPGTGPKLLIY GNNNRP ADI-14375 Light chain variable region

S GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDTSLSVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 44 87 EVQLVESGGGLVQPGGSLRLSCAASG FTFSSYWMH WVRQAPGKGPVWVS RINSD ADI-14376 Heavy chain variable region

GSTTNYADYMKG RFTISRDNAKNTVYLQMNSLRAEDTAVYYC ARDSDSYDDAFDI (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 44 88 SYELTQPPSVSVSPGQTARISC SGEALPKKYSY WYQQKSGQAPVLVIY EDSKRPS GIP ADI-14376 Light chain variable region

ERFSGSSSGTMATLTISGAQVEDEADYYC YSTDSSGNHRV FGGGTKVTVL (“LC”) amino acid sequence

Ab 45 89 EVQLVESGGGVVQPGGSLRLSCAVSG ITFSSYGMH WVRQAPGKGLEWVA FIRYD ADI-14377 Heavy chain variable region

GSNKYYGDSLRG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKDAVGIGGYYGLD (“HC”) amino acid sequence

V WGQGTTVTVSS

Ab 45 90 DIQMTQSPSSLSASVGDRVTITC RASQGIRNDLG WYQQKPGKAPKRLIY AASSLQS ADI-14377 Light chain variable region

GVPSRFSGSGSGTEFTLTISSLQPEDFATYYC LQHNGYPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 46 91 QVQLVESGGGLVQPGGSLRLSCAASG FTFSSYWMH WVRQAPGKGLVWVS RINS ADI-14378 Heavy chain variable region

DGSSPTYADSVKG RFTISRDNAKNTVFLQMNSLRAEDTAVYYC ARESWELIRGDAF (“HC”) amino acid sequence

DI WGQGTTVTVSS

Ab 46 92 DIQMTQSPSSLSASVGDRVTITC RASQSISSSLN WYQQKPGKAPNLLIY AASTLQS G ADI-14378 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYRTPRT FGQGTKVEIK (“LC”) amino acid sequence

Ab 47 93 EVQLLESGGGVVQPGRSLRLSCAASG FTFSSYAMH WVRQAPGKGLEWVA VIGND ADI-14379 Heavy chain variable region

GTNKYHADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARRRVGIMYSGSY (“HC”) amino acid sequence

WGGMDV WGQGTTVTVSS

Ab 47 94 SYELTQPPSVSVSPGQTASITC SGDKLGGKYVS WYQQKPGQSPVLVMY QDTRRPS ADI-14379 Light chain variable region

GIPERLSGSNSGSTATLTISATQAMDEADYYC QAWDITTVHVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 48 95 QVQLVQSGAEVKKPGESLKISCKGSG YTFTSYWIG WVRQLPGKGLEWMG VIFPGD ADI-14380 Heavy chain variable region

SDTRYSPSFQG QVTISADKSISTAYLQWSSLKAADTAMYYC ARTRLGRGFYRFDS W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 48 96 QSVLTQPPSVSAAPGQKVTISC SGSSSNIGNNYVS WYQQLPGTAPRLLIY ENNERPS ADI-14380 Light chain variable region

GIPDRFSGSKSGTSATLGITGLQTGDEADYYC ATWDSGLSAGYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 49 97 EVQLVESGGGLVQPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS YIGSSS ADI-14381 Heavy chain variable region

SSVYYGDSAKG RFTISRDNAKNSLYLQMNSLRDEDTALYYC ARVGWLQYCRGGSCY (“HC”) amino acid sequence

ASFGMDV WGQGTTVTVSS

Ab 49 98 DIQMTQSPSSLSASVGDRVTITC RASQGIRNDLG WYQQKPGIAPKLLIY AASSLQS G ADI-14381 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC LQDYDSPYT FGQGTKLEIK (“LC”) amino acid sequence

Ab 50 99 EVQLLESGGGVVQPGRSLRLSCAASG FTFSAYGFH WVRQAPGKGLEWVA VIWFD ADI-14382 Heavy chain variable region

GNNKYYADSMKG RFIISRDNSKNTLYLQMNSLRAEDTAVYYC ARDPKETGEFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 50 100 QSALTQPASVSGSPGQSITISC TGTISDVGRYNYVS WYQQHPGKAPKLMIY DVTNR ADI-14382 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEAVYYC CSYTISSTYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 51 101 QITLKESGPTLVKPTQTLTLTCTFSG FSLSTSGVGVG WIRQPPGKALEWLA LIYWDE ADI-14383 Heavy chain variable region

DKRYSPSLKT RLTITKDTSRNQVKLTMTNMDPVDTATYYC AHQYYDILTGYPSPGAF (“HC”) amino acid sequence

DI WGQGTTVTVSS

Ab 51 102 QPVLTQPASVSGSPGQSITISC TGTSSDVVSYNLVS WFQQHPGKAPKLMIY EVTRRP ADI-14383 Light chain variable region

S GVSNRFSGSKSGNTASLTISGLQAEDEADYYC CAYTGTPVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 52 103 QVQLQESGSGLVKPSQTLSLTCTVSG GSISSVGYSWS WIRQPPGKGLEWIG YIYHSG ADI-14384 Heavy chain variable region

SPYYSPSLNS RVTISVDRSKNQFSLKLSSVTAADTAVYFC ARVFFGGGGAFDI WGQG (“HC”) amino acid sequence

TTVTVSS

Ab 52 104 QPGLTQPPSVSVAPGQTARITC GGNNIGSKSVQ WYQQKPGQAPVLVMY YDSDRP ADI-14384 Light chain variable region

S GIPDRFSGSSSGNTATLTITRVEAGDEADYSC QVWDSVNVHPVI FGGGTKLTVL (“LC”) amino acid sequence

Ab 53 105 QVQLVQSGAEVKKPGESLKISCKGSG YSFTSYWIG WVRQMPGKGLEWMG IIYPGD ADI-14385 Heavy chain variable region

SDTRYSPSFQG QVTISADKSISTAYLQWSSLKASDTAMYYC ASSSYSNYFDY WGQG (“HC”) amino acid sequence

TLVTVSS

Ab 53 106 NFMLTQPHSVSESPGKTVTISC TRSSGSIASNYVQ WYQQRPGSAPTTVIY EDNQRP ADI-14385 Light chain variable region

S GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDSSNPWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 54 107 EVQLVESGGGLVQPGGSLRLSCAASR FTFSSYAMS WVRQAPGKGLEWVS GIGASG ADI-14386 Heavy chain variable region

GTTYYADSVKG RFTISRDNSKNTVYLQMNSLRAEDTAVYYC ARCEYYYGSGSAGYYF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 54 108 SYELTQPPSVSVSPGQTASITC SGDKLGSKFAF WYQQKPGQSPVLVIF QDVKRPS GI ADI-14386 Light chain variable region

PERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSGTAV FGGGTKVTVL (“LC”) amino acid sequence

Ab 55 109 EVQLVESGGGVVQPGRSLRLSCAASG FTFSSYPMH WVRQAPGKGLEWVA VISYD ADI-14388 Heavy chain variable region

GSNKYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYSC ARAQSAAIFDH WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 55 110 QAVVTQEPSLTVSPGGTVTLTC ASSTGAVTSGYYPN WFQQKPGQAPRALIY TTSKR ADI-14388 Light chain variable region

HS WTPARFSGSLLGGKAALTLSGVQPEDEADYYC LLYYGGANWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 56 111 EVQLVESGGGLVKPGGSLRLSCAASG FTFINAWMA WVRQAPGKGPEWVG RIKSR ADI-14389 Heavy chain variable region

ADGGTTDYAAPVKG RFTISRDDSKNRLFLQMDSLKTDDTAVYFC TTGVRALRFYNG (“HC”) amino acid sequence

MDV WGQGTTVTVSS

Ab 56 112 ETTLTQSPSSLSASIGDRVTITC RAGQSISSFLN WYQQKPGKAPKLLIY AASTLQS GVP ADI-14389 Light chain variable region

SRFSGSKSGTDFTLTISSLQPEDFATYYC QQSYHTFT FGPGTKVEIK (“LC”) amino acid sequence

Ab 57 113 QVQLVESGPGLVKPSETLSLTCAVSG YSISSGYYWG WIRQPPGKGLEWIG NIYHSGS ADI-14390 Heavy chain variable region

TYYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARATLRFTLVREVVVTACD (“HC”) amino acid sequence

AFDI WGQGTTVTVSS

Ab 57 114 QSALTQPASVSGSPGQSITISC TGTSSDVGSYNLVS WYQQHPGKVPKLVIY EVNKRP ADI-14390 Light chain variable region

S GVSNRFSGSKSGNTASLTISGLQAEDEADYYC CSYAGSSTFVV EGGGTKLTVL (“LC”) amino acid sequence

Ab 58 115 QVQLVESGGGLVQPGGSLRLSCAAAG FSFSNYAMS WVRQAPGKGLEWVA VISGN ADI-14391 Heavy chain variable region

AGSTYYAESVKG RFTISRDNSKNTLHLQMNSLRGEDTAVYYC AKPPGIAVAGEYYW (“HC”) amino acid sequence

YFDL WGRGTLVTVSS

Ab 58 116 QVQLMQPPSVSVSPGQTARITC SGDALPRENAY WYQQKSGQAPVLVIY EDSKRPS ADI-14391 Light chain variable region

GIPERFSGSSSGTMATLTITGAQVEDEADYYC YSTDTSAYHWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 59 117 EVQLLESGAEVKKPGSSVKVSCKASG GTFSSYGIS WVRQAPGQGLEWMG GIIPIFG ADI-14392 Heavy chain variable region

TSNYAQKFQG RVTITADESTSTAYMELSSLRSEDTAVYYC ALDSSGRARYYAMDV W (“HC”) amino acid sequence

GQGTTVTVSS

Ab 59 118 DIQVTQSPATLSLSPGERATLSC RASQSVSSYLA WYQQKPGQAPRLLIY DASNRAT G ADI-14392 Light chain variable region

IPARFSGSGSGTDFTLTISSLEPEDFAVYYC QQRNNWPPT FGPGTKVEIK (“LC”) amino acid sequence

Ab 60 119 QVQLVESGGGLVKPGGSLRLSCAASG FSFTGFYMN WVRQAPGKGLEWVS SISSSS ADI-14393 Heavy chain variable region

TYKNYADSLQG RFTISRDNARSSLYLQMNSLRAEDTAVYYC ARTRTEYTYGYYHDF (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 60 120 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQVPGTAPKLLIY NNNN ADI-14393 Light chain variable region

RPS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSRLSGV FGGGTKLTVL (“LC”) amino acid sequence

Ab 61 121 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-14394 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARGSEYYFDY WGQGTL (“HC”) amino acid sequence

VTVSS

Ab 61 122 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-14394 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSVV EGGGTKVTVL (“LC”) amino acid sequence

Ab 62 123 EVQLVESGGGVVQPGRSLRLSCAASG FTFSSYAMH WVRQAPGKGLEWVA VISYD ADI-14395 Heavy chain variable region

GSNKYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDDTYYYDSSGYS (“HC”) amino acid sequence

APFDY WGQGTLVTVSS

Ab 62 124 DIQVTQSPSTLSASVGDRVTITC RASQSISSWLA WYQQKPGKAPKLLIY KASSLES GV ADI-14395 Light chain variable region

PSRFSGSGSGTEFTLTISSLQPDDFATYYC QQYNSYPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 63 125 EVQLVESGGGVVQPGRSLRLSCAASG FTFSSYAMH WVRQAPGKGLEWVA VISYD ADI-14396 Heavy chain variable region

GSNKYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARELRYFDWEYGG (“HC”) amino acid sequence

MDV WGQGTTVTVSS

Ab 63 126 EIVLTQSPSSLSASVGDRVTITC QASQDISNYLN WYQQKPGKAPKLLIY DASNLET GV ADI-14396 Light chain variable region

PSRFSGSGSGTDFTFTISSLQPEDIATYYC QQYDNLPMYT FGQGTKLEIK (“LC”) amino acid sequence

Ab 64 127 EVQLVESGGGVVQPGRSLRLSCAASG FTFSSYAMH WVRQAPGKGLEWVA VISYD ADI-14397 Heavy chain variable region

GSNKYYADSVK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDDTYYYDSNGYS (“HC”) amino acid sequence

APFDY WGQGTLVTVSS

Ab 64 128 DIQVTQSPSTLSASVGDRVTITC RASQSISSWLA WYQQKPGKAPKLLIY KASSLES GV ADI-14397 Light chain variable region

PSRFSGSGSGTEFTLTISSLQPDDFATYYC QQYNSYPWT FGQGTKVDIK (“LC”) amino acid sequence

Ab 65 129 EVQLLESGPGLVKPSQTLSLTCAVSG GSINSGRYSWS WIRQPPGKGLEWIG YIYYSG ADI-14399 Heavy chain variable region

TTYYNPSLES RVTISRDTSKNQFSLNLSSVTAADTAVYYC ARTNSADSYASGSHYIRP (“HC”) amino acid sequence

QYFDF WGQGTLVTVSS

Ab 65 130 DIQLTQSPATLSLSPGERATLSC RASQSVSSYLA WYQQKPGQAPRLLIY GASNRAT GI ADI-14399 Light chain variable region

PARFSGSGSGTDFTLTISRLEPEDFAVYYC QQRSNWLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 66 131 QVQLVQSGGGVVQPGRSLRLSSAASG FTFSSYAMH WVRQAPGKGLEWVA VISHD ADI-14400 Heavy chain variable region

GSKYYADSVKG RFTISRDNSKSTLNLQMNSLRPEDTAVYYC ARGGDVRLYDDSNGY (“HC”) amino acid sequence

HYDTYYFDY WGQGTLVTVSS

Ab 66 132 EIVLTQSPSSLSASVGDRVTITC RASQGIRNDLG WYQQKPGKAPKLLIY AASTLQS GV ADI-14400 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC LQDYNYPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 67 133 QVQLVQSGGGLVKPGGSLRLSCAASG FTFSSYSMH WVRQAPGKGLEWVS SISASS ADI-14401 Heavy chain variable region

SYLNYADSVKG RFTISRDNAKKSLYLQLNTLRADDTAVYYC AREDHDSGTYYLNWF (“HC”) amino acid sequence

DP WGQGTLVTVSS

Ab 67 134 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQFPGTGPKLLIY GNSHR ADI-14401 Light chain variable region

PS GVPDRFSGSKSGPSASLAITGLQAEDEADYYC QSYDSSLSGYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 68 135 QVQLVQSGAEVKKPGASVKVSCKTSG YTFTNYGIS WVRQAPGQGLEWMG WISAY ADI-14402 Heavy chain variable region

NGNRNYAQKLQG RVTMTTDTSTSTAYMELRSLRSDDTAVYYC AREPPVIAAGDFS (“HC”) amino acid sequence

H WGQGTLVTVSS

Ab 68 136 EIVLTQSPLSLPVTLGQPASISC RSSQSLVHSDANTYLS WFQQRPGQSPRRLIY KVSN ADI-14402 Light chain variable region

RDS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQGTHWPPD FGQGTRLEIK (“LC”) amino acid sequence

Ab 69 137 QVQLVESGGGLGKPGGSLRLSCAASG FTFSGYYMS WIRQAPGKGLEWVS DISSGSS ADI-14403 Heavy chain variable region

FTNYADSVKG RFTISRDNAKNSLYLQMNSLKAEDTAVYYC ARVPPDSYGSGSYSGD (“HC”) amino acid sequence

S WGQGTLVTVSS

Ab 69 138 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYGVH WYQQLPGTAPKLLIY GNTNR ADI-14403 Light chain variable region

PS GVPDRISGSKSGTSASLVITGLQAEDEADYYC QSYDSSLSGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 70 139 EVQLVESGGGLVQPGGSLRLSCAASG FTFSNFEMN WVRQAPGKGLEWVS YISSSG ADI-14404 Heavy chain variable region

RIIYYADSVKG RFTISRDNARNSLYVQMNSLRVEDTAVYYC ARAKAAAGHDL WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 70 140 EIVLTQSPSTLSASVGDRVTITC RASQSISPWLA WYQQKPGKAPKLLIY RASSLES GV ADI-14404 Light chain variable region

PSRFSGSGSGTEFTLTISSLQPDDFATYYC QHYNSYLYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 71 141 QVQLVQSGTEVKKPGASVKVSCKASG YTFTNYDIS WVRQAPGQGLEWMG WISGS ADI-14405 Heavy chain variable region

TGNTIYAQNLQG RLTMTTDTSTSTAYMELRSLRSDDTAIYYC ARDNVGYASGNYFD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 71 142 SYVLTQPPSVSVAPGKTARIPC GGNNIGSKSVH WYQQRPGQAPVLVIY YDSVRPS G ADI-14405 Light chain variable region

IPERFSGSNSGNTATLTISTVEAGDEADFYC QVWDSSRDHEV FGGGTKLTVL (“LC”) amino acid sequence

Ab 72 143 QVQLVQSGAEVKKPGESLKISCKGSG YKFTNYWIA WVRQMPGKGLEWLG VIYPGA ADI-14406 Heavy chain variable region

SDITYSPSFQG QVTISADKSISTAYLQWSSLKASDTAIYYC ARQGSITAMSY WGQGT (“HC”) amino acid sequence

MVTVSS

Ab 72 144 DIVMTQSPLSLPVTPGEPASISC RSSQSLLHSNGFNYLD WYLQKPGQSPQLLIY LGSN ADI-14406 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPFT FGPGTKVEIK (“LC”) amino acid sequence

Ab 73 145 QVQLVQSGGGVVQPGRSLRLSCAASG FTFSSYGMH WVRQAPGKGLEWVA VIWF ADI-14407 Heavy chain variable region

DGNNKEYADSVKG RFAISRDNSKNTLYLQMNSLRAEDTAVYYC ARDLIPVTIFGVV (“HC”) amino acid sequence

NPYSYYGMDV WGQGTTVTVSS

Ab 73 146 EIVMTQSPSSLSASVGDRVTITC RASQSISTYLN WYQQKPGTAPKLLIY AASSLES GV ADI-14407 Light chain variable region

PSRLSGSGSGTEFILTISSLQREDFATYYC QQSYSTPPT FGQGTKVEIK (“LC”) amino acid sequence

Ab 74 147 QVQLVQSGPALVKITQTLTLICTFSG FSLITSGMCVS WIRQPPGKALEWLA RIDW ADI-14408 Heavy chain variable region

DDDKYYSTSLKT RLTISKDTSKNQVVLTLTNVDPVDTATYYC ARMQKYDSSGYYLHY (“HC”) amino acid sequence

FDS WGQGTLVTVSS

Ab 74 148 DIRLTQSPSSLSASVGDRVTIAC RASQSISSYLN WYQQKPGKSPKVLIY AASILQT GVP ADI-14408 Light chain variable region

SRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSINQYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 75 149 QVQLVQSGGEVKKPGASVKVSCKASG YTFTYYGIS WVRQAPGQGLEWMG WISAY ADI-14409 Heavy chain variable region

NGNTNYEQKFQG RVTMTTDTSTGTAYMELRSLTSDDTAVYYC ARDRIVVVTAANY (“HC”) amino acid sequence

YGLDV WGQGTTVTVSS

Ab 75 150 DIQLTQSPDSLAVSLGERATINC KSSQSVLYRPNNKNFLA WYQQKPGQPPKLLIY W ADI-14409 Light chain variable region

ASTRQS GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC QQYHTTPLT FGGGTKVDIK (“LC”) amino acid sequence

Ab 76 151 QVQLQQWGAGLLKPSETLSLICAIYS GSFSGYYWS WIRQPPGKGLEWIG QINYSGS ADI-14410 Heavy chain variable region

AYYTPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARVRITMVQGAIVPCAIDV (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 76 152 SYELTQPPSASGTPGQRVTISC SGSSSNIESNFVY WYQQLPGTAPKLLIH RNDQRPS ADI-14410 Light chain variable region

GVPDRFSGSKSGTSASLAISGLRSEDEADYSC AAWDDSLSGVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 77 153 QVQLVQSGAEVKKPGASVKLSCKASG YTFTRFYIH WVRQAPGQGLEWMG IINPSG ADI-14411 Heavy chain variable region

GGTSYAQNFQD RVTMTRDTSTSTVYMELSSLRSEDTAVYYC ARNGYSTRSLQNNW (“HC”) amino acid sequence

FDP WGQGTLVTVSS

Ab 77 154 ETTLTQSPSSLSASVGDRVTITC RASQSIDNYLN WYQQKPGKAPKLLIY EASSLQS GV ADI-14411 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQTYSSLPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 78 155 QVQLVQSGAEVKKPGASVKVSCKASG YTFTRYGIS WVRQAPGQGLEWMG WISDY ADI-14412 Heavy chain variable region

NGNTKNAEKFQG RVTMTTDTYTNIAYMELRSLRSDDTAVYYC ARDWWITVGGIIA (“HC”) amino acid sequence

PFDY WGQGTLVTVSS

Ab 78 156 ETTLIQSPGILSLSPGERATLSC RASQSVSSDYLA WFQQKPGQAPRLLIY GASSRAT ADI-14412 Light chain variable region

DIPDRFSGSGSGTDFTLTISRLESEDFAVYYC LHYAGART FGQGTKVEIK (“LC”) amino acid sequence

Ab 79 157 EVQLVESGGVVVQPGGSLRLSCAASG FNFDDYSMH WVRQAPGKGLEWVS VISW ADI-14413 Heavy chain variable region

DGGITYYADSVKG RFTMSRDNGKKSLYLQMNSLRTEDTAVYYC GKDGDIYSSSSAG (“HC”) amino acid sequence

IDY WGQGTLVTVSS

Ab 79 158 SYVLTQPPSASGTPGQRVIISC SGSSSNIGSHTVK WYQQLPGTAPKLLID RNNQRPS ADI-14413 Light chain variable region

GVPDRFSGPKSGTSASLAISGLQSEDEADYYC ASWDDSLNGPV FGGGTQLTVL (“LC”) amino acid sequence

Ab 80 159 QVQLVQSGAEVKKPGSSMKVSCKASG GSFSSYGIS WLRQAPGQAPEWMG GIIPIF ADI-14414 Heavy chain variable region

GTINYAQKFQG RITISADESTSTVYMELSSLRIEDTAVYYC ARDGRTSPRYYGWDV W (“HC”) amino acid sequence

GQGTTVTVSS

Ab 80 160 DIRLTQSPATLSLSPGDRATLSC RASQSLYTYLS WYQQKPGQAPRLLIY DASNRAT GI ADI-14414 Light chain variable region

PARFSGSGSGTDFTLTISSLEPEDFAVYYC HYRSNWPPCT FGGGTKVDIK (“LC”) amino acid sequence

Ab 81 161 EVQLVESGPGLVKPSETLSLTCTVSG GSISNYYWT WIRQPPGEGLEWIG YIYYTGST ADI-14415 Heavy chain variable region

NYNPSLKN RVTISVDTPKNQFSLKLNSVTAADTAVYYC ARGWGYSYGYESYYNGLD (“HC”) amino acid sequence

V WGQGTTVTVSS

Ab 81 162 DIQLTQSPSFLSASVGDRVTITC RASQGISSYLA WYQLKPGKAPKLLIY AAATLET GVP ADI-14415 Light chain variable region

SRFSGSGSGTEFTLTISGLQPEDFATYYC QQLNSFPFT FGPGTKVEIK (“LC”) amino acid sequence

Ab 82 163 QVQLVQSGAEVKKPGESLKISCKGSG DTFSRNWIG WVRQMPGKGLEWMG IIWP ADI-14416 Heavy chain variable region

GDSDTRYRQFFQGQQG QVIISVDKSISTAYLQWSSLKASDTATYYC ATSPYGLGSYY (“HC”) amino acid sequence

EH WGQGTLVTVSS

Ab 82 164 NFMLTQPHSLSDSPGKTVVISC TRSSGSIASNYVQ WYQQRPGSAPTTVIY EDNQRP ADI-14416 Light chain variable region

S GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDSSNPYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 83 165 EVQLVESGGGLVKPGGSLRLSCAASG FSFSSYSMH WVRQAPGKGLEWVS SISGSST ADI-14417 Heavy chain variable region

YIYHADSVKG RFTISRDNAERSLHLQMNSLRAEDTAVYYC ARDPYSSGWLDS WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 83 166 ETTLTQSPATLSVSPGERATLSC RASQSVSGNLA WYQQKPGQAPRLLIY GTSTRAT G ADI-14417 Light chain variable region

IPARFSGSGSGTEFTLSISSLQSEDFAVYYC QQYNKWPRYT FGQGTKLEIK (“LC”) amino acid sequence

Ab 84 167 QVQLVQSGAEVKKPGSSVKVSCKASG GTFTNYNIN WVRQAPGQGLQWMG RISP ADI-14418 Heavy chain variable region

TFAIANYAQKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYC ARAPHSGYDLALDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 84 168 DIQMTQSPSTLSASVGDRVTITC RASQSISSWLA WYQQKPGKAPKLLIY EASSLQS G ADI-14418 Light chain variable region

VPSRFSGSGSGTEFTLTITSLQPDDFATYYC QQYNVYPWT FGQGTKVDIK (“LC”) amino acid sequence

Ab 85 169 EVQLVESGGGVVQPGGSLRLSCAASG FSFSDYGMH WVRQAPGKGLEWVS FIRYD ADI-14419 Heavy chain variable region

ASYKFYADSVKG RFTISRDNAKNTLYLQINSLRAEDTAVYYC AKEIYGSGSYYYYYYAI (“HC”) amino acid sequence

DV WGQGTTVTVSS

Ab 85 170 EIVLTQSPGTLSLSPGERATLSC RASQSVSSSHLA WYQQKPGQAPRLLIY GASSRAT G ADI-14419 Light chain variable region

IPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYFRSAWA FGQGTKVDIK (“LC”) amino acid sequence

Ab 86 171 EVQLVESGGVVVQPGGSLRLSCAASG FNFDDYAMH WVRQAPGKGLEWVS LISW ADI-14420 Heavy chain variable region

DGGNTYYSDSVKG RFTISRDNGKNSLYLQMNSLRAEDTALYYC AKDIDRYSGYDYV (“HC”) amino acid sequence

FHY WGQGTLVTVSS

Ab 86 172 DIRLTQSPSTLSAYVGDRVTITC RASQSISSWLA WYQQKPGKAPKLLIY KASSLES GV ADI-14420 Light chain variable region

PSRFTGSGSGTEFTLTISGLQPDDFATYYC QQYNSYST FGGGTKVDIK (“LC”) amino acid sequence

Ab 87 173 QVQLVQSGAEVKKPGESLKISCKGSG YNSSINWIGYWIG WVRQMPGKGLEWMG I ADI-14421 Heavy chain variable region

INPGDSDTRYSPSFQG QVTISVDKSISTAYLQWGSLKASDTAMYYC ARRAYRSGWH (“HC”) amino acid sequence

FDL WGRGTLVTVSS

Ab 87 174 EIVMTQSPATLSVSPGERATLTC RASQSVSSNLA WYQQKPGQAPRLLIY GASTRAT ADI-14421 Light chain variable region

GIPARFSGSGSGTQFTLTISSLQSEDFAVYYC QHYNNWPPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 88 175 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYTIN WVRQAPGQGLEWMG RIIPIL ADI-14422 Heavy chain variable region

GIANYAQKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYC ARRHQDTYGMDV WG (“HC”) amino acid sequence

QGTTVTVSS

Ab 88 176 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-14422 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV FGGGTKVTVL (“LC”) amino acid sequence

Ab 89 177 EVQLVESGGVVIQPGGSLRLSCAASG FNFDDYSMH WVRQAPGKGLEWVS LISWD ADI-14423 Heavy chain variable region

GGITYYADSVKG RFTISRDNGKKSLYLQMNSLRTEDTALYYC AKDIDIYSDYAGYFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 89 178 DIRMTQSPSSLSASVGDRVTITC RASQGIRNDLG WYQQKPGKAPKRLIY AASSLQS G ADI-14423 Light chain variable region

VPSRFSGSGSGTEFTLTISSLQPEDFATYYC LQHNSYPFT FGQGTRLEIK (“LC”) amino acid sequence

Ab 90 179 QVQLVQSGAEVKKPGESLKISCKGPD SSFSVYWIA WVRQMPGKGLEWMG VIYVG ADI-14424 Heavy chain variable region

DSDTRYSPSFRG QVTISADKSMNTAYLQWSSLKASDTAMYFC ARHIPPGPFDL WG (“HC”) amino acid sequence

QGTMVTVSS

Ab 90 180 NFMLTQPHSVSASPGKTITISC TRSSGSIASNSVQ WYQQRPGSAPTNVIY EDDQRPL ADI-14424 Light chain variable region

GVPNRFSGSIDSSSNSASLTISGLKTEDEADYYC HSYHNSDQV FGGGTKLTVL (“LC”) amino acid sequence

Ab 91 181 QVQLQESGPGLVKPSETLSLTCTVSG GSVRSGSYYWS WIRQPPGKALEWIG YIYYSG ADI-14425 Heavy chain variable region

STNYNPALES RVTISVDTSKNQFSLMLSSVTAADTAVYYC ARSAEGLARLYYFDH WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 91 182 QSVLIQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIH DVSNR ADI-14425 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC STYRSSNTLVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 92 183 EVQLVESGGGVVQPGRSLRLSCAASG FTFSSFPMH WVRQAPGKGLEWVA VASYD ADI-14426 Heavy chain variable region

GRNNYYAGSVKG RFTISRDNSKNTLYLQINSLRAEDTAVYYC AREVVIAAHFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 92 184 SSELTQEPAVSVALGQTVRITC QGDSLRSFYAN WYQQKPGQAPILVIY GKNDRPS GI ADI-14426 Light chain variable region

PDRFSGSNSGNTASLTITGAQAEDEADYYC NSRDSSGNHRV FGGGTKVTVL (“LC”) amino acid sequence

Ab 93 185 QVQLVQSGAEVKKPGSSVKVSCKASG GTFNSYTIN WVRQAPGQGLEWMG RIITIP ADI-14427 Heavy chain variable region

GATNYAQKFQG RVTFTADKSTSTAYMELSSLRSEDTAVYFC AKRGTGYYGMDV W (“HC”) amino acid sequence

GQGTTVTVSS

Ab 93 186 QSVLIQPRSVSGSPGQSVTISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY DVSER ADI-14427 Light chain variable region

PS GVPDRFSGSKSGNTASLTISGLQAEDEADYYC CSFVGIYILV FGGGTKLTVL (“LC”) amino acid sequence

Ab 94 187 EVQLLESGGGLVKPGGSLRLSCAASG FTFSDHYMS WIRQAPGKGLEWVS YISSTSSF ADI-14428 Heavy chain variable region

TNYADSLKG RFTISRDNAKNSLYLQMNSLRAEDTAVYY CARPYIVALGTRAFDI WG (“HC”) amino acid sequence

QGTTVTVSS

Ab 94 188 SYVLIQPPSVSVAPGKTARITC GGNNIGSKTVH WYQQKPGQAPVLVSY YDSDRPS G ADI-14428 Light chain variable region

IPERFSGSNSGNTATLTISRVEAGDEADYYC QVWDGSSEHYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 95 189 QVQLVQSGTEVKKPGSSVKVSCKASG GTFSSYTIS WVRQAPGQGLEWMG GITPM ADI-14564 Heavy chain variable region

VGTPNYAQKFQG RVAITADKSTNTAYMELTSLISGDTAVYYC ARLVYGSGSHFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 95 190 SSELSQDPAVSVALGQTVRITC QGDSLRSFYAS WYQQQPGQAPVLVLY GQDNRPS ADI-14564 Light chain variable region

GIPDRFSGSSSGNTASLTITGAQAEDEADYYC NSRNSSGHHWV FGGGTKVTVL (“LC”) amino acid sequence

Ab 96 191 EVQLLESGGGLVKPGGSLRLSCAASG FTFSNAWMS WVRQAPGKGLEWVG RIKSKT ADI-14565 Heavy chain variable region

DGGTTDYAAPVKG RFTISRDDSKNTLYLQMNSLKTEDTAVYYC TTDRFCSSTSCEYY (“HC”) amino acid sequence

YYYYGMDV WGQGTTVTVSS

Ab 96 192 ETTLIQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIY AASSLQS GV ADI-14565 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 97 193 QVQLLESGGGVVQPGRSLRLSCAASG FTFSSFPMH WVRQAPGKGLEWVA VASYD ADI-14566 Heavy chain variable region

GRNNYYAGSVKG RFTISRDNSKNTLYLQINSLRAEDTAVYYC AREVVIAAHFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 97 194 SSELTQEPAVSVALGQTVRITC QGDSLRSFYAN WYQQKPGQAPILVIY GKNDRPS GI ADI-14566 Light chain variable region

PDRFSGSNSGNTASLTITGAQAEDEADYYC NSRDSSGNHRV FGGGTKVTVL (“LC”) amino acid sequence

Ab 98 195 QVQLVQSGAEVKKPGASVRVSCKASG YTFNSYSIS WVRQAPGQGLEWMG WISVH ADI-14567 Heavy chain variable region

NGNTNYTQKFQG RVTMTTDTSTSTTYMELRSLRSDDTAVYYC IFGELLYDV WGQG (“HC”) amino acid sequence

TTVTVSS

Ab 98 196 DIQLTQSPSSLSASVGDRVTITC RASQGISNYLA WYQQKPGKVPNLLIY AASTLQS G ADI-14567 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDVATYYC QKYNSAPLT FGPGTKVEIK (“LC”) amino acid sequence

Ab 99 197 EVQLVESGGGVVQPGRSLRLSCAASG FTFSSYGMH WVRQAPGKGLEWVA VIWYD ADI-14568 Heavy chain variable region

GSNKYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDIAAAGTMRAFD (“HC”) amino acid sequence

I WGQGTTVTVSS

Ab 99 198 QSVLIQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY DVSNR ADI-14568 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSTLVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 100 199 QVQLVESGGGFVKPGGSLRLSCAASG FTFSDYYMS WIRQAPGKGLEWLS YISSTSLF ADI-14569 Heavy chain variable region

TYYADSVKG RFTISRDNAKNSLYLQMNSLRADDTAVYYC ARAYGKGTMVGY WGQ (“HC”) amino acid sequence

GTMVTVSS

Ab 100 200 EIVMTQSPGTLSLAPGERATLSC RASQSVSIDYLA WYQHKPGQAPRLLIY TASNRAT ADI-14569 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDVAMYYC QQYGNSPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 101 201 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSTYTIT WVRQAPGQGLEWMG RIVPIF ADI-14571 Heavy chain variable region

GVVNNAQKFLG RLTITADKSTSTAYMELSSLRSEDTAVYYC ARIPCSGNCQDYYYG (“HC”) amino acid sequence

MDV WGQGTTVTVSS

Ab 101 202 DIQLTQSPSFLSASVGDRVTITC RASQGISSYLV WYQQKPGKAPKLLIY AASTLQS GV ADI-14571 Light chain variable region

PSRFSGSGSGTEFTLTISSLQPEDFATYYC QQLNNYPPT FGPGTKVDIK (“LC”) amino acid sequence

Ab 102 203 QVQLVQSGGGLVKPGGSLRLSCAASG FTFSNAWIS WVRQAPGKGLEWVG RIKSAT ADI-14572 Heavy chain variable region

DGGTTDYAAPVKG RFTISRDDSKNTLYLQMDSLKTEDTAVYYC TTSYPYFDWLPFSV (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 102 204 SYELMQPPSASGTPGQRVTISC SGSNSNIGSNTVS WYQQLPGTAPKLLIY NNNQRP ADI-14572 Light chain variable region

S GVPDRFSGSKSGTSASLAISGLQSEDEADYYC ATWDDSLNGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 103 205 QVQLVQSGAEVKKPGASVKVSCKASG YTFTTYGIS WVRQAPGQGLEWMG WISTY ADI-14573 Heavy chain variable region

KTYTNYAQKFQG RVTMTTDTSTSTAYMELRSLRSDDTAVYYC AKVAGGSGSYGDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 103 206 QPVLTQPPSVSVAPGKTARITC GGNNIGSKSVH WYLQKPGQAPVLVIY YDSDRPS GI ADI-14573 Light chain variable region

PERFSGSNSGNTATLTISRVEAGDEADFFC QVWDSSSDHWV FGGGTKVTVL (“LC”) amino acid sequence

Ab 104 207 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYTIS WVRQAPGQGLEWMG RIIPILG ADI-14575 Heavy chain variable region

IANYAQKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYC ARPSSSSFAFDY WGQGT (“HC”) amino acid sequence

LVTVSS

Ab 104 208 QSVLTQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY DVSNR ADI-14575 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSTPVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 105 209 QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYGIS WVRQAPGQGLEWMG WISAY ADI-14576 Heavy chain variable region

NGNTNYAQKLQG RVTMTTDTSTSTAYMELRSLRSDDTAVYYC ARDPPVIAAGDFQ (“HC”) amino acid sequence

H WGQGTLVTVSS

Ab 105 210 DIVLTQSPLSLPVTLGQPASISC RSSQSLVHSDGNTYLN WFQQRPGQSPRRLIY KVS ADI-14576 Light chain variable region

NRDS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQGTHWPPD FGQGTRLEIK (“LC”) amino acid sequence

Ab 106 211 QVQLVQSGAEVKKPGASVKVSCKASG YTFTNYGIT WVRQAPGQGLEWMG WISA ADI-14577 Heavy chain variable region

YNGVRNYAQKLQG RVTMTIDTSRTTAYMELKNLRSDDTAMYYC ARGPPVIAADDF (“HC”) amino acid sequence

QHW GQGTMVIVSS

Ab 106 212 DIQMTQSPLSLPVTLGQPASISC RSSQSLVHSNGDTYLN WFQQRPGRSPRRLIY KVS ADI-14577 Light chain variable region

NRDS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQGTHWPPD FGQGTRLEIK (“LC”) amino acid sequence

Ab 107 213 QVQLVQSGAEVKKPGSSVKVSCKASG GTFNNYAIN WVRQAPGQGLEWMG GIIP ADI-14578 Heavy chain variable region

MFGTANYAQKFQG RVTMTADESTSTAYMELSSLRSEDTAVYYC ASSQIFVGGNYY (“HC”) amino acid sequence

KLEFDN WGQGTLVTVSS

Ab 107 214 QSVLTQPPSVSAAPGQKVTISC SGSNSNIGYNDVS WYQQLPGTAPQLLIY DNNKRT ADI-14578 Light chain variable region

S GIPDRFSGSKFGTSATLGITGLQTGDEADYYC GTWDSSLSTVI FGGGTKLTVL (“LC”) amino acid sequence

Ab 108 215 QVQLVQSGAEVKKPGESLKISCKVSG YSFTSYWIG WVRQMPGKGLEWMG IIYPGD ADI-14579 Heavy chain variable region

SDTRYSPSFQG QVTISADKSITTAYLQWSSLKASDTAMYYC ARPAHSSSWYGAFDL (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 108 216 DIQMTQSPSSLSASVGDRVTITC RASQGISNYLA WYQQKPGKVPKLLIY AASTLQS G ADI-14579 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDVATYYC QKYNSAPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 109 217 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYTIN WVRQAPGQGLEWMG RIIPVL ADI-14580 Heavy chain variable region

GMASYVQNFQG RVSITADESTSTAYMELSSLTSEDTALYYC AKGAVAAANDVFDV (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 109 218 DIQMTQSPDSLAVSLGERATINC KSSQSVFYSSNNKHYLA WYQQKPGQPPKLLFY ADI-14580 Light chain variable region

WASTRES GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC QQYYRIPYT FGQGTKVEI (“LC”) amino acid sequence

K

Ab 110 219 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSHAFS WVRQAPGQGLEWMG GIIPSL ADI-14581 Heavy chain variable region

NTANYAQKFQG RVSITADESTGTAYMELSSLRSDDTAVYFC AREVFGYGYYFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 110 220 ETTLTQSPATLSVSPGERATLSC RASQNVNSNLA WYQQKPGQAPRLLIY GASTRAT ADI-14581 Light chain variable region

GIPARFSGSGSGTDFTLTISSLQSEDFAVYYC QQYNMWPPFT FGQGTKLEIK (“LC”) amino acid sequence

Ab 111 221 QVQLVQSGAEVKKPGESLKISCKGPD SSFSVYWIA WVRQMPGKGLEWMG VIYVG ADI-14582 Heavy chain variable region

DSDTRYSPSFRG QVTISADKSINTAYLQWSSLKASDTAMYFC ARHIPPGPFDL WGQ (“HC”) amino acid sequence

GTTVTVSS

Ab 111 222 NFMLTQPHSVSASPGKTITISC TRSSGSIASNSVQ WYQQRPGSAPTNVIY EDNQRPL ADI-14582 Light chain variable region

GVPNRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYHSSDQV FGGGTKVTVL (“LC”) amino acid sequence

Ab 112 223 QVQLVQSGAEVKEPGASVKVSCKASG YTFTNYGIS WVRQAPGQGLEWLG WISAY ADI-14583 Heavy chain variable region

NGNIHYAQKVQG RVTMTTDTSTSTGFMELRSLRSDDTAVYYC AREPPVIAAGDFQ (“HC”) amino acid sequence

H WGQGTLVTVSS

Ab 112 224 ETTLTQSPLSLPVTLGQPASISC RSSQSLVHSNGNTYLS WFQQRPGQSPRRLIY RVSN ADI-14583 Light chain variable region

RDS GVPDRFSGSGSGTDFTLKISRVEAEDVGLYYC MQGTHWPPD FGQGTRLEIK (“LC”) amino acid sequence

Ab 113 225 QVQLVQSGAEVKKPGASVKVSCKASG FTFTNYGTSYGIT WVRQAPGQGLEWMG ADI-14584 Heavy chain variable region

WINTSNGNPNYAQKLQG RVTMTADTSTSTAYMELRSLISDDTAVYYC ARGHRMV (“HC”) amino acid sequence

RGVVPTGYYGLDV WGQGTTVTVSS

Ab 113 226 DIQLTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIF AASNLQS GV ADI-14584 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYITPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 114 227 QVQLVQSGAEVKKPGASVKVSCKASG YTFANYGIG WVRQAPGQGLEWMG WISA ADI-14585 Heavy chain variable region

YNGKTNYAQKFQG RVTMTTDTSTSTAYMELRSLRSDDTAVYYC AREPPVIAAGDFP (“HC”) amino acid sequence

H WGQGTLVTVSS

Ab 114 228 ETTLTQSPLSLPVTLGQPASISC RSSQSLEHSDLNTYLS WFQQRPGQSPRRLIY KVSN ADI-14585 Light chain variable region

RDS GVPDRFSGSGSGTDFTLRISRVEAEDVGVYYC MQGTHWPPD FGQGTRLEIK (“LC”) amino acid sequence

Ab 115 229 QVQLVQSGGGLVKPGGSLRLSCAASG FTFSDYYMS WIRQAPGKGLEWVS YISSSSS ADI-14586 Heavy chain variable region

YTNYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AKRTEYCSSTGCAYYFD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 115 230 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-14586 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV FGGGTKVTVL (“LC”) amino acid sequence

Ab 116 231 EVQLLESGGGLVKPGGSLRLSCAASG FTLTSYSMN WVRQAPGKGLEWVS SISSSSS ADI-14587 Heavy chain variable region

YIHYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AGSSLYPPFFDY WGQG (“HC”) amino acid sequence

TLVTVSS

Ab 116 232 QSVVTQPPSVSGAPGQRVTISC TGSSSNLGAGYDVH WYQQLPGTAPKLLIY GNNN ADI-14587 Light chain variable region

RPS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSSVV EGGGTKLTVL (“LC”) amino acid sequence

Ab 117 233 QVQLVQSGAEVKKPGASVKVSCKVSG DTLTELSIH WVRQAPGKGHEWMG YFDHE ADI-14588 Heavy chain variable region

DGEIMYAQKFQG RVTMTGDTSTDTAYMELSSLRSEDTAVYYC ATVAAAGQFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 117 234 DIQLTQSPSSLSASVGDRVTITC RARQSISTYLN WYQQKPGKAPKLLIY AASSLQS GV ADI-14588 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSSPYT FGQGTKVDIK (“LC”) amino acid sequence

Ab 118 235 QITLKESGPVLVKPSETLTLTCTVSG FSLSNAKMGVS WIRQPPGKALEWLA HIFSND ADI-14589 Heavy chain variable region

EKSYNTSLKN RLTISKDTSKSQVVLTMTNMDTVDTATYYC ARINYYDSSGYYLANFD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 118 236 NIRLTQSPSSLSASVGDRVTITC RASQRIASYLN WYQQKPGHAPKLLIH AASSLQS GV ADI-14589 Light chain variable region

PSRFSGSGSGTDFTLTINSLLPEDFATYYC QQSYSSPPHSSPPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 119 237 EVQLVESGAEVKKPGESLKISCKGSG YSFATYWIG WVRQMPGKGLEWMG IIYPGD ADI-14590 Heavy chain variable region

SDTRYSPSFQG QVTISADKSISTAYLQWSSLKASDTAIYYC ARAKLPVAGLYYFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 119 238 DIQLTQSPSSLSASVGDRVTITC RASQGISSTLA WYQQKPGKAPKLLIY DASSLES GV ADI-14590 Light chain variable region

PSRFSGSGSGTDFTLTISSLHPEDFATYYC QQFNTYPT FGGGTKVEIK (“LC”) amino acid sequence

Ab 120 239 QVQLVQSGAEVKKPGESLRISCTGSG YTFTNYWIS WVRQMPGKGLEWMG RIDPT ADI-14591 Heavy chain variable region

DSYTNYSPSFQG HVTISADKSISTAYLQSSSLKASDTATYYC ARHRRLVPAAMSRGYY (“HC”) amino acid sequence

GMDV WGQGTTVTVSS

Ab 120 240 EIVMTQSPSSLSASVGDRATITC RASQSISSYLN WYQQKPGKAPKLLIY AASNLQS GA ADI-14591 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYFC QQTYSTPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 121 241 QVQLVQSGAEVKKPGESLKISCKGSG YTFTNYWIG WVRQMPGKGLEWMG IIYPD ADI-14592 Heavy chain variable region

DSDTRYSPSFQG QVTISVDKSINTAYLQWSSLRASDTAIYYC ACSNWPHYFDS WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 121 242 NFMLTQPHSVSESPGKTVTISC TRSSGNIAGNYVQ WYQQRPGSAPTTVIY EDNQRP ADI-14592 Light chain variable region

S GVPDRFSGSIDSSSNSASLTISGLKTEDEAVYYC QSYHPGNWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 122 243 QVQLVQSGAEVKKPGESLKISCKGSG YSFSSYWVA WVRQMPGKGLEWMG IIYPA ADI-14593 Heavy chain variable region

DSDTRYSPSFQG QVTISADKSDSTAYLQWGSLKASDTAMYYC ARSLYGSGDYFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 122 244 NFMLTQPHSVSESPGRTVIISC TRSSGSIATNYVQ WYQQRPGSAPTTVIY EDNQRPS ADI-14593 Light chain variable region

GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYGSGDVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 123 245 QVQLVQSGAEVKKPGASVKLSCKASG YTFTTYTIN WVRQAPGQGLEWMG WISGY ADI-14594 Heavy chain variable region

NGNTDYAQKLQG RFTMTIDTSTNTAYMELRSLTSDDTAVYYC AKGGGGSESYFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 123 246 SYELTQPPSVSVAPGKTARISC GGNNIGSKSVH WYQQKPGQAPVLVIY YDRDRPS GI ADI-14594 Light chain variable region

PERFSGSNSGNTATLTISRVEAGDEADYYC QLWDRSSDHPYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 124 247 EVQLLESGGGLVQPGGSLRLSCAASG FTFSIYSMN WVRQAPGKGLEWIS YISRSGST ADI-14595 Heavy chain variable region

IFYADSVKG RFTISRDDAKNSLFLQMTSLRDADTAVYYC ARVDCSNNKCYDY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 124 248 DIQLTQSPATLSLSPGERATLSC RASQSISSFLA WYQQKPGQAPRLLIY DASKRAT GT ADI-14595 Light chain variable region

PARFSGGGSGRDFTLTISSLEPEDFAVYYC QQRSSWPLYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 125 249 EVQLVESGGVVVQPGGSLRLSCAVSG FNFDDYSMH WVRQLPGKGLEWVS LISWD ADI-14597 Heavy chain variable region

GGITYYADSVKG RFTISRDNSKNSLYLQMNSLRTEDTALYYC AKDGNRYSDNDYYFD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 125 250 DIRLTQSPGILSLSPGERATLSC RASQGVSSSYLA WYQQKPGQAPRLLIY GASSRAT ADI-14597 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPL FGPGTKVEIK (“LC”) amino acid sequence

Ab 126 251 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYAIY WVRQAPGQGLECMG GIIPIFG ADI-14598 Heavy chain variable region

SANYAQKFQG RVTITADESTSTAYMELSSLRSEDTAVYYC ATDSLKTTYYYGSSGYFR (“HC”) amino acid sequence

DHV WGQGTTVTVSS

Ab 126 252 ETTLTQSPSSLSASVGDRVTITC RASQGISNYLA WYQQKPGKVPKLLIF AASTLQS GV ADI-14598 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDVATYYC QNFNSVLSFT FGPGTKVDIK (“LC”) amino acid sequence

Ab 127 253 EVQLVESGGGLVQPGRSLRLSCKTSG FTFGDYAMS WVRQAPGQGLDWVG FIRTK ADI-14599 Heavy chain variable region

AYGGTTEYAASVKG RFTLSRDDSKSIAYLQMNSLKTEDTAVYYC KSGGQFDY WGR (“HC”) amino acid sequence

GTLVTVSS

Ab 127 254 NFMLTQPHSVSGSPGKTVTISC TGSSGSIASNYVQ WYQQRPGSAPTTVIC EDNQRP ADI-14599 Light chain variable region

S GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDRSNQEV FGGGTKLTVL (“LC”) amino acid sequence

Ab 128 255 QVQLVQSGGGLVKPGGSLRLSCAASG FSFSDYYMN WIRQAPGKGLEWVS YISSSSS ADI-14600 Heavy chain variable region

YTNYADSVKG RFTISRDNAKKSLYLQMNSLRAEDTAVYYC ASQTYSDYARGGAFDI (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 128 256 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNNNR ADI-14600 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV FGIGTKVTVL (“LC”) amino acid sequence

Ab 129 257 EVQLLESGGGLVQPGGSLRLSCAASG FTFSSYAMN WVRQAPGKGLEWVS TISGSG ADI-14601 Heavy chain variable region

SSTYYADSVEG RFTISRDNSKNTLYLQMNSLRAEDTAIYYC AKEPRDMYIQQWLDS (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 129 258 GIRLTQSPSSVSASVGDRVIITC RASQGIRSWLA WYQQKPGKAPKLLIY AASRLQS G ADI-14601 Light chain variable region

VPSRFSGSGSETDFTLTISSLQPEDFASYYC QQANSFPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 130 259 EVQLVESGGGVVQPGGSLRLSCAASG FSFSSCGMH WVRQVSGKGLEWVA FIRYD ADI-14602 Heavy chain variable region

GSNKFYADSVKG RFTISRDNSKNTLYLQMNSLRVEDTAVYYC AKGGLEDVSTGYSP (“HC”) amino acid sequence

HYYYGMDV WGQGTTVTVSS

Ab 130 260 QPVLTQPPSVSVSPGQTASITC SGDKLAYKYTC WYQQKPGQSPVLVIF QDSKRPS GI ADI-14602 Light chain variable region

PERFSGSNSGNTATLTISGTQALDEADYYC QAWDSSTVVF GGGTKLTVL (“LC”) amino acid sequence

Ab 131 261 QVQLVQSGAEVKKPGESLKISCKGSG YTFTNYWIG WVRQMPGKGLEWMG IIYPG ADI-14603 Heavy chain variable region

DSDTRYSPSFQG QVTISADKSITTAYLQWRVLKASDTAMYYC ATMRGSSSHFHH W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 131 262 DIQVTQSPSSLSASVGDRVTITC RAGQGIGNYLA WYQQKPGKVPKVLIY AASTLQS G ADI-14603 Light chain variable region

VPSRFSGSGSGTEFTLTISSLQPEDVATYYC QKYNNAPYA FGQGTRLEIK (“LC”) amino acid sequence

Ab 132 263 EVQLLESGGGLVQPGGSLRLSCSASG FTFNNYVMH WVRQAPGKGLEDAS AISSNG ADI-14604 Heavy chain variable region

VSTNYADSVKG RFTISRDNSKNTLYLQMRSLRAEDTALYYC VRDLIPHDSSAYYGYH (“HC”) amino acid sequence

GMDV WGQGTTVTVSS

Ab 132 264 QPVLTQPPSASGTPGQSVTISC SGSSSNIGTNVVN WYQQLPGTAPKLLIY SNDLRPS ADI-14604 Light chain variable region

GVPDRFSGSKSGTSASLAISGLQSEDEANYYC AAWDDSLNGVL FGGGTKLTVL (“LC”) amino acid sequence

Ab 133 265 EVQLLESGPALVKPTQTLTLICTFSG FSLTTSGMCVS WIRQPPGKALEWLA RIDWD ADI-14605 Heavy chain variable region

DDQYFSTSLRT RLSISKDTSKNQVVLTMTNMDPVDTATYYC ARSALNIAARGFDI W (“HC”) amino acid sequence

GQGTTVTVSS

Ab 133 266 QPGLTQPPSVSVSPGQTARITC SGDVLPKHFSY WYQQKPGQAPVLVIH RDSERPS G ADI-14605 Light chain variable region

IPERFSGSSSGTTVTLTISGVQAEDEADYYC QFSDITNTV FGGGTKLTVL (“LC”) amino acid sequence

Ab 134 267 QVQLVQSGGGLVQPGGSLRLSCAASG FTVSSNYMG WVRQAPGKGLEWVS VIYTG ADI-14606 Heavy chain variable region

GSTYYADSVKG RFTISRDNFKNTLYLQMNSLRAEDTALYYC ARDLYSSGWFGY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 134 268 DIRLTQSPATLSVSPGERATLSC RASQSVSINLG WFQQKPGQSPRLLIY GTSTRAT GI ADI-14606 Light chain variable region

PARFSGSGSGTEFTLTISSLQSEDFAVYYC HQYNNWPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 135 269 EVQLLESGGGVVQSGRSLRLSCAASG FTFNNYAMH WVRQAPGKGLEWVA VISFD ADI-14607 Heavy chain variable region

GGNKFYGDSVQG RFTISRDNSKNTLYLQTNSLRPEDTAVYYC ARDRWEIQIGLDI W (“HC”) amino acid sequence

GQGTTVTVSS

Ab 135 270 SYVLTQPPSVSVSPGQTARITC SGDALARQNAY WYQQKPGQAPVLVMY RDTGRPS ADI-14607 Light chain variable region

GIPERFSGSSSGTTVTLTISEVQAEDEADYYC QSADSSGAYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 136 271 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-19420 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARVGWGYSYGYWFDP (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 136 272 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-19420 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 137 273 EVQLLESGGGVVQPGRSLRLSCAASG FTFSSYGMH WVRQAPGKGLEWVA VISYD ADI-19421 Heavy chain variable region

GSNKYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKDIHHVLRFLDPDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 137 274 QSVLIQPASVSGFPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY EVSNR ADI-19421 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSTLV FGGGTKLTVL (“LC”) amino acid sequence

Ab 138 275 EVQLVESGGGVVQPGRSLRLSCAASG FTFSSYGMH WVRQAPGKGLEWVA VISYD ADI-19422 Heavy chain variable region

GSNKYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKEGYNWNDYYFD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 138 276 QPVLTQPPSVSVAPGKTARITC GGNNIGSKSVH WYQQKPGQAPVLVVY DDSDRPS ADI-19422 Light chain variable region

GIPERFSGSNSGNTATLTISRVEAGDEADYYC QVWDSSSDHWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 139 277 EVQLLESGGGLVQPGGSLRLSCAASG FTVSSNYMS WVRQAPGKGLEWVS DIYSGG ADI-19424 Heavy chain variable region

RTDYADSVKG RFTISRDNSKNTLDLQMNSLRAEDTAVYYC ARETLGMDHWYFDL (“HC”) amino acid sequence

WGRGTLVTVSS

Ab 139 278 QPGLTQPPSVSVAPGKTARITC GGNNIGSKSVH WYQQKPGQAPVLVVY DDSDRPS ADI-19424 Light chain variable region

GIPERFSGSNSGNTATLTISRVEAGDEADYYC QVWDSTSDHPV FGGGTKLTVL (“LC”) amino acid sequence

Ab 140 279 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-19425 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARLGYCSGGSCHFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 140 280 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-19425 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGFYV FGIGTKLTVL (“LC”) amino acid sequence

Ab 141 281 QVQLQESGPGLVKPSETLSLTCTVSG GSISSYYWS WIRQPPGKGLEWIG YIYYSGST ADI-19426 Heavy chain variable region

NYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARGNEELGTGSNWFDP WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 141 282 SYVLTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY QDSKRPS GI ADI-19426 Light chain variable region

PERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 142 283 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-19427 Heavy chain variable region

FISYADSVKG RFTISRDSAKNSLYLQMNSLRAEDTAVYYC ARDHPNWNGLAYFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 142 284 QSVLTQPPSISGAPGQRVTISC TGSSSNIGAGYDVQ WHQQLPGTAPKLLIY GNSNR ADI-19427 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 143 285 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-19428 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDSCSGGSCYSPRFDP (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 143 286 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-19428 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSTVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 144 287 EVQLQESGPGLVKPSETLSLTCTVSG GSISSSSYYWG WIRQPPGKGLEWIG SIYYSGS ADI-19429 Heavy chain variable region

TYYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARTPLYSYGRVVGFYYYGM (“HC”) amino acid sequence

DV WGQGTTVTVSS

Ab 144 288 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-19429 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 145 289 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYTIS WVRQAPGQGLEWMG RIIPILG ADI-19430 Heavy chain variable region

IANYAQKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYC ARDGGPYYYDSSGYYRL (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 145 290 DIRMTQSPLSLPVTLGQPASISC RSSQSLVYSDGNTYLN WFQQRPGQSPRRLIY KVS ADI-19430 Light chain variable region

NRDS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQGTHWTYT FGQGTKLEIK (“LC”) amino acid sequence

Ab 146 291 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-19431 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARELYDYVWGSYRDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 146 292 QPGLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-19431 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV FGGGTKVTVL (“LC”) amino acid sequence

Ab 147 293 QVQLVQSGAEVKKPGASVKVSCKVSG YTLTELSMH WVRQAPGKGLEWMG GFDP ADI-19432 Heavy chain variable region

EDGETIYAQKFQG RVTMTEDTSTDTAYMELSSLRSEDTAVYYC ATEREEGGYSGYD (“HC”) amino acid sequence

DAFDI WGQGTMVTVSS

Ab 147 294 DIRMTQSPSTLSASVGDRVTITC RASQSISSWLA WYQQKPGKAPKLLIY KASSLES G ADI-19432 Light chain variable region

VPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQYNSYSYT FGQGTKLEIK (“LC”) amino acid sequence

Ab 148 295 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-19433 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARAPPSVGGWYFDL W (“HC”) amino acid sequence

GRGTLVTVSS

Ab 148 296 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-19433 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLV FGGGTKLTVL (“LC”) amino acid sequence

Ab 149 297 QVQLQESGPGLVKPSQTLSLTCTVSG GSISSGSYYWS WIRQPAGKGLEWIG RIYTSG ADI-19435 Heavy chain variable region

STNYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC AREGRGGAFDI WGQGTL (“HC”) amino acid sequence

VTVSS

Ab 149 298 SYELTQPPSVSVSPGQTARITC SADALPKQYAY WYQQKPGQAPVLVIY KDSERPS GI ADI-19435 Light chain variable region

PERFSGSSSGTTVTLTISGVQAEDEADYYC QSADSSGTYVV FGGGTQLTVL (“LC”) amino acid sequence

Ab 150 299 QVQLVQSGPGLVKPSETLSLTCTVSG GSISSSSYYWG WIRQPPGKGLEWIGS IYYSG ADI-19436 Heavy chain variable region

STYYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARSLMNYSNYVLGFDP W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 150 300 QPVLTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY QDSKRPS G ADI-19436 Light chain variable region

IPERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 151 301 EVQLVQSGAEVKKPGASVKVSCKASG YTFTSYGIS WVRQAPGQGLEWMG WISAY ADI-19437 Heavy chain variable region

NGNTNYAQKLQG RVTMTTDTSTSTAYMELRSLRSDDTAVYYC ARDGIAAAGTLFD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 151 302 DIQLTQSPSSVSASVGDRVTITC RASQGISSWLA WYQQKPGKAPKLLIY AASSLQS G ADI-19437 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQANSFPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 152 303 EVQLVESGGGLVQPGGSLRLSCAASG FTFSSYAMS WVRQAPGKGLEWVS AISGSG ADI-19439 Heavy chain variable region

GSTYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKYSNYGSFDY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 152 304 DIQMTQSPSTLSASVGDRVTITC RASQSISSWLA WYQQKPGKAPKLLIY KASSLES G ADI-19439 Light chain variable region

VPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQYNSYST FGQGTKVEIK (“LC”) amino acid sequence

Ab 153 305 EVQLVESGGGLVQPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS YISSSSS ADI-19440 Heavy chain variable region

TIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREGYSGSYGYYFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 153 306 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-19440 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV FGIGTKLTVL (“LC”) amino acid sequence

Ab 154 307 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYAIS WVRQAPGQGLEWMG RIIPILG ADI-19441 Heavy chain variable region

IANYAQKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYC ARGPLTGYSSSWFDP W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 154 308 EIVMTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIY AASSLQS GV ADI-19441 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTLPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 155 309 QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYGIS WVRQAPGQGLEWMG WISAY ADI-19444 Heavy chain variable region

NGNTNYAQKLQG RVTMTTDTSTSTAYMELRSLRSDDTAVYYC ARDEALVGATFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 155 310 DIVMTQSPDSLAVSLGERATINC KSSQSVLYSSNNKNYLA WYQQKPGQPPKLLIY W ADI-19444 Light chain variable region

ASTRES GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC QQYYSTPRT FGQGTKVEIK (“LC”) amino acid sequence

Ab 156 311 EVQLVESGPGLVKPSGTLSLTCAVSG GSISSSNWWS WVRQPPGKGLEWIG EIYHSG ADI-19445 Heavy chain variable region

STNYNPSLKS RVTISVDKSKNQFSLKLSSVTAADTAVYYC ARDVETDGYNYGYYFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 156 312 SYELIQPPSVSVAPGKTARITC GGNNIGSKSVH WYQQKPGQAPVLVVY DDSDRPSG ADI-19445 Light chain variable region

IPGRFSGSNSGNTATLTISRVEAGDEADYYC QVWDSSSDHKV FGGGTKLTVL (“LC”) amino acid sequence

Ab 157 313 QVQLQESGPGLVKPSETLSLICTVSG GSISSSSYYWG WIRQPPGKGLEWIG SIYYSG ADI-19447 Heavy chain variable region

STYYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARDRVVTTYFDY WGQGT (“HC”) amino acid sequence

LVTVSS

Ab 157 314 SYELTQPPSVSVSPGQTARITC SGDALPKKYAY WYQQKSGQAPVLVIY EDSKRPS GI ADI-19447 Light chain variable region

PERFSGSSSGTMATLTISGAQVEDEADYYC YSTDSSGNHRV FGGGTKLTVL (“LC”) amino acid sequence

Ab 158 315 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-19448 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARELLDPGIAAAGFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 158 316 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-19448 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSVNYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 159 317 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-19449 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDSGSYLSYAFDI WGQ (“HC”) amino acid sequence

GTMVTVSS

Ab 159 318 SYELTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNRP ADI-19449 Light chain variable region

S GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 160 319 EVQLLESGGGLVQPGGSLRLSCAASG FTFSSYWMH WVRQAPGKGLVWVS RINSD ADI-19450 Heavy chain variable region

GSSTSYADSVKG RFTISRDNAKNTLYLQMNSLRAEDTAVYYC ARAPISILRFLGGYFD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 160 320 EIVMTQSPSTLSASVGDRVTITC RASQSISSWLA WYQQKPGKAPKLLIY KASSLES GV ADI-19450 Light chain variable region

PSRFSGSGSGTEFTLTISSLQPDDFATYYC QQYNSYSS FGQGTKLEIK (“LC”) amino acid sequence

Ab 161 321 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-19454 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARGYCSGGSCYSHYFQH (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 161 322 QSVLTQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY DVSNR ADI-19454 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSTVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 162 323 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-19455 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARSQSGSYYSSDY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 162 324 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-19455 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGWV FGGGTKVTVL (“LC”) amino acid sequence

Ab 163 325 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-19457 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARQGYCSGGSCYHIDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 163 326 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-19457 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 164 327 EVQLVESGGGRVKPGGSLRLSCAASG FTFRSYSMN WVRQAPGKGLEWVS SISSSSS ADI-19458 Heavy chain variable region

YINYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDGSGMTIFGVVIDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 164 328 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-19458 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDRSLTVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 165 329 QVQLVESGGGLVQPGGSLRLSCAASG FTVSSNYMS WVRQAPGKGLEWVS VIYSG ADI-19459 Heavy chain variable region

GSTYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AREALGMDHWYFDL (“HC”) amino acid sequence

WGRGTLVTVSS

Ab 165 330 SYELMQPPSVSVAPGKTARITC GGNNIGSKSVH WYQQKPGQAPVLVVY DDSDRPS ADI-19459 Light chain variable region

GIPERFSGSNSGNTATLTISRVEAGDEADYYC QVWDSSSDHPV FGGGTKVTVL (“LC”) amino acid sequence

Ab 166 331 QVQLQQWGAGLLKPSETLSLTCAVYG GSFSGYYWS WIRQPPGKGLEWIG EINHSG ADI-19460 Heavy chain variable region

STNYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARGGITAYYYYYGMDV W (“HC”) amino acid sequence

GQGTTVTVSS

Ab 166 332 DIQMTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIY AASSLQS G ADI-19460 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 167 333 EVQLVESGGGLVKPGGSLRLSCAASG FTFSDYYMS WIRQAPGKGLEWVS YISSSGS ADI-19461 Heavy chain variable region

TIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ASSLTVTSRSDAFDI WG (“HC”) amino acid sequence

QGTMVTVSS

Ab 167 334 QPGLTQLPSVSVAPGKTARITC GGNNIGSKSVH WYQQKPGQAPVLVVY DDSDRPS ADI-19461 Light chain variable region

GIPERFSGSNSGNTATLTISRVEAGDEADYYC QVWDSSSDHVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 168 335 QITLKESGPTLVKPTQTLTLTCTFSG FSLSTSGVGVG WIRQPPGKALEWLA LIYWDD ADI-19462 Heavy chain variable region

DKRYSPSLKS RLTITKDTSKNQVVLTMTNMDPVDTATYYC AHAANWGYYFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 168 336 DIVMTQSPSTLSASVGDRVTITC RASQSISSWLA WYQQKPGKAPKLLIY KASSLES G ADI-19462 Light chain variable region

VPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQYNSYWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 169 337 QVQLQESGPGLVKPSQTLSLTCTVSG GSISSGDYYWS WIRQPPGKGLEWIG YIYYSG ADI-19463 Heavy chain variable region

STYYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARDRLGIFDY WGQGTLVT (“HC”) amino acid sequence

VSS

Ab 169 338 EIVLTQSPDSLAVSLGERATINC KSSQSVLYSSNNKNYLA WYQQKPGQPPKLLIY WA ADI-19463 Light chain variable region

STRES GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC QQYYSTPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 170 339 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-19465 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREGSSSWYYFDY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 170 340 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-19465 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGPWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 171 341 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-19467 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ASLSSSSELGYYFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 171 342 QPVLTQPPSVSGAPGQRVTISCT GSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-19467 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 172 343 EVQLVESGPGLVKPSETLSLICTVSG GSISSSSYYWG WIRQPPGKGLEWIG SIYYSGS ADI-19468 Heavy chain variable region

TYYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARRDGYNYGWFDP WGQG (“HC”) amino acid sequence

TLVTVSS

Ab 172 344 NFMLTQPHSVSESPGKTVTISC TGSSGSIASNYVQ WYQQRPGSAPTTVIY EDNQRP ADI-19468 Light chain variable region

S GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDSSNVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 173 345 QVQLQESGPGLVKPSETLSLTCAVSG YSISSGYYWG WIRQPPGKGLEWIG SIYHSGS ADI-19469 Heavy chain variable region

TYYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARWTVMYYFDY WGQGTL (“HC”) amino acid sequence

VTVSS

Ab 173 346 EIVMTQSPATLSLSPGERATLSC RASQSVSSYLA WYQQKPGQAPRLLIY DASNRAT G ADI-19469 Light chain variable region

IPARFSGSGSGTDFTLTISSLEPEDFAVYYC QQRSNWPT FGGGTKLEIK (“LC”) amino acid sequence

Ab 174 347 EVQLLESGGGVVQPGRSLRLSCAASG FTFSSYGMH WVRQAPGKGLEWVA VISYD ADI-19470 Heavy chain variable region

GSNKYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKGRGDFWSGYGM (“HC”) amino acid sequence

DV WGQGTTVTVSS

Ab 174 348 SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY QDSKRPS GI ADI-19470 Light chain variable region

PERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTAV FGGGTKVTVL (“LC”) amino acid sequence

Ab 175 349 EVQLVESGGGLVQPGGSLRLSCSASG FTFSSYAMH WVRQAPGKGLEYVS AISSNG ADI-19471 Heavy chain variable region

GSTYYADSVKG RFTISRDNSKNTLYLQMSSLRAEDTAVYYC VKADQGSSGWFPDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 175 350 NFMLTQPHSVSESPGKTVTISC TRSSGSIASNYVQ WYQQRPGSSPTTVIY EDNQRPS ADI-19471 Light chain variable region

GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDSSNWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 176 351 EVQLVESGAEVKKPGESLKISCKGSG YSFTSYWIG WVRQMPGKGLEWMG IIYPGD ADI-19473 Heavy chain variable region

SDTRYSPSFQG QVTISADKSISTAYLQWSSLKASDTAMYYC ARLIAAAGIDY WGQG (“HC”) amino acid sequence

TLVTVSS

Ab 176 352 NFMLTQPHSVSESPGKTVTISC TRSSGSIASNYVQ WYQQRPGSSPTTVIY EDNQRPS ADI-19473 Light chain variable region

GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDSSNIWV FGGGTKVTVL (“LC”) amino acid sequence

Ab 177 353 QVQLVQSGAEVKKPGESLKISCKGSG YSFTSYWIG WVRQMPGKGLEWMG IIYPGD ADI-19474 Heavy chain variable region

SDTRYSPSFQG QVTISADKSISTAYLQWSSLKASDTAMYYC ARPYSGSYYAFDI WGQ (“HC”) amino acid sequence

GTTVTVSS

Ab 177 354 NFMLTQPHSVSESPGKTVTISC TRSSGSIASNYVQ WYQQRPGSSPTTVIY EDNQRPS ADI-19474 Light chain variable region

GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDSSNQV FGGGTKLTVL (“LC”) amino acid sequence

Ab 178 355 EVQLLESGAEVKKPGASVKVTCKASG YTFTHFGIN WVRQAPGQGLEWLG WISAYN ADI-19475 Heavy chain variable region

GNTNYVQKIQG RVTMTTDTSTNTAYMELRSLRSDDTAVYYC ARGPPVEAAGTFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 178 356 DIVLTQSPLSLPVTLGQPASISC RSSQSLVYSDGNTYLT WFQQRPGQSPRRLIY KVSN ADI-19475 Light chain variable region

RDS GVPDRFSGSGSGTDFTLQISRVEAEDVGVYYC MQGTHWPFT FGPGTKVEIK (“LC”) amino acid sequence

Ab 179 357 QVQLVESGPTLVKPTQTLTLTCTFSG FSLSTSRVGVG WIRQPPGKALEWLA LIYWD ADI-19476 Heavy chain variable region

DDKRYSPSLKS RLTITKDTSKNQVVLTMTNMDPVDTARYYC AHRSTYDILGGYYYFD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 179 358 QPVLTQPRSVSGSPGQSVTISC TGTSSDVGGYNYVS WFQQHPGKAPKLMIY DVSK ADI-19476 Light chain variable region

RPS GVPNRFSGSKSGNTASLTISGLQAEDEADYFC CSYAGTYEV FGGGTKLTVL (“LC”) amino acid sequence

Ab 180 359 QVQLVESGPGVVKPSETLSLICTVSG GPVSSRSYYWG WIRQPPGKGLEWIG SIYYS ADI-19478 Heavy chain variable region

GSTYYNTSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC AKLQYSTSGFDY WGQG (“HC”) amino acid sequence

TLVTVSS

Ab 180 360 QPVLTQPPSVSEAPRQRVTISC SGSSSNIGNNAVS WYQQLPGKAPKLLIY YDDLVPS ADI-19478 Light chain variable region

GVSDRFSGSKSGTSASLAISGLQSEDEADYYC AAWDDSLNGVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 181 361 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSNAIN WVRQAPGQGLEWMG GIIPIF ADI-19479 Heavy chain variable region

GTANYAQKFQG RVTITTDESTSTAYMELSSLRSEDTAVYYC ATTFYYGSGADY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 181 362 DIQMTQSPLSLPVTLGQPASISC RSSQSLVYSDGNMYLS WFQQRPGQSPRRLIY KVS ADI-19479 Light chain variable region

NRDS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQGTHWWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 182 363 EVQLVESGGGLVKPGGSLRLSCAASG FTFSAYSMN WVRQAPGKGLEWVS SISSTT ADI-19480 Heavy chain variable region

NYISYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDPKYYGLGTYYKDD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 182 364 NFMLTQPHSVSESPGKTVTISC TRSGGSIASNYVQ WYQQRPGSSPTTVIY EDNQRP ADI-19480 Light chain variable region

S GVPDRFSGSIDSSFNSASLTVSGLKTEDEADYYC QSFDNNNRWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 183 365 EVQLVESGGVVVQPGGSLRLSCAASG FTFDDYTMH WVRQAPGKGLEWVS LISWD ADI-19481 Heavy chain variable region

GGITYYADSVKG RFTISRDNSKNSLYLQMNSLRTEDTALYYC VKGGYYDGSGYYYFD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 183 366 DIQMTQSPSSLSASVGDRVTVTC RASQSISSYLN WYQHKPGNAPKLLIY AASSLQS G ADI-19481 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 184 367 QVQLQQWGAGLLKPSETLSLTCGAFH GSFSGYYWS WIRQPPGKGLEWIG EVTHSR ADI-19482 Heavy chain variable region

STNYNPSLKS RITISVDTSRNQFSLKLNSVTAADTAVYYC ARGSGEWYFDI WGRGTL (“HC”) amino acid sequence

VTVSS

Ab 184 368 DIQLTQSPSTLSASVGDRVTITC RASQSISSWLA WYQQKPGRAPKLLIY KASSLES GV ADI-19482 Light chain variable region

PSRFSGSGSGTEFTLTISSLQPDDFATYYC QQYNSYSPEI FGQGTKVEIK (“LC”) amino acid sequence

Ab 185 369 QVQLVQSGAEVKKPGESLKISCKGSG YSFTTYWIG WVRQMPGKGLEWMG IIFPGD ADI-19483 Heavy chain variable region

SDTRYSPSFQG QVTISADKSISTAYLQWSSLKASDTAMYFC ARSAFPFGFDI WGQG (“HC”) amino acid sequence

TMVTVSS

Ab 185 370 SYVLTQPHSVSESPGKTVTISC TRSSGSIASNYVQ WYQQRPGSSPTTVIY EDHQRPS ADI-19483 Light chain variable region

GVPDRFSGSIDSSSNSASLTISGLQTEDEADYYC QSYGSGNPWV FGGGTKVTVL (“LC”) amino acid sequence

Ab 186 371 QVQLQESGSGLVKPSQTLSLTCVVSG GSISSGGNSWS WIRQPPGKGLEWIG YIYDS ADI-19484 Heavy chain variable region

GNTYYNPSLKS RVTISVDRSKNQFSLKVSSVTAADTAVYYC ARGAETGTTGWYDP W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 186 372 DIRLTQSPSSLSASVGDRVTITC RASQTISSYLNWY QQKPGKAPRLLIY AASSLQS GV ADI-19484 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYGTPRT FGQGTKVEIK (“LC”) amino acid sequence

Ab 187 373 QVQLQESGPGLVKPSQTLSLSCTVSG GSISSTNYYWT WIRQHPGKGLEWIG FIYNR ADI-19485 Heavy chain variable region

GSTYYNPSLTS RVTISVDTSKNQFSLKLTSVTAADTAVYYC ARAPYYYDRNGYYTAFD (“HC”) amino acid sequence

I WGQGTTVTVSS

Ab 187 374 EIVLTQSPATLSVSPGERATLSC RASQSVSSNLA WYQQKPGQAPRLLIY DASTRAT DI ADI-19485 Light chain variable region

PARFSGGGSGTEFTLTISSLQSEDFAVYYC QQYNNWPRT FGLGTKVDIK (“LC”) amino acid sequence

Ab 188 375 QVQLQESGPGLVKPSETLSLTCSVSG GSLTSYYWS WIRQPPGKGLEWIG YIYYSGST ADI-19486 Heavy chain variable region

NYNPSLKS RLTISVDTSKNQFSLKLSSVTAADTAVYYC ARVGGRGVINVFDY WGQG (“HC”) amino acid sequence

TLVTVSS

Ab 188 376 QPVLTQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY EVSNR ADI-19486 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC DSYRSNSASVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 189 377 QVTLKESGPALVKPTQTLTLTCTFSG LSISTSGMCVS WIRQPPGKALEWLA RIDWD ADI-19487 Heavy chain variable region

DDKYYSTSLKT RLTISKDTSKNQVVLTMTNMDPVDTATYYC ARINYYDSSGYYVYYF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 189 378 DIQMTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIY AASSLQS G ADI-19487 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPPFT FGPGTKVDIK (“LC”) amino acid sequence

Ab 190 379 QVQLVQSGAEVKKPGASVKVSCKVSG YTLTELSMH WVRQAPGKGLEWMG GFDP ADI-19488 Heavy chain variable region

EDGETIYAQKFQG RVTMTEDTSTDTAYMELSSLRSEDTAVYYC ATARFLEWLSGTN (“HC”) amino acid sequence

WFDP WGQGTLVTVSS

Ab 190 380 DIQLTQSPLSLPVTPGEPASISC RSSQSLLHSNGYNYLD WYLQKPGQSPQLLIY LGSN ADI-19488 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPPT FGGGTKVEIK (“LC”) amino acid sequence

Ab 191 381 QITLKESGPALVKPTQTLTLTCT FSGFSLSTSGMCVS WIRQPPGKALEWLA RIDWDD ADI-19489 Heavy chain variable region

DKYYSTSLKT RLTISKDTSKNQVVLTMTNMDPVDTATYYC ARMCWGNYVPIDAFDI (“HC”) amino acid sequence

WGQGTMVTVSS

Ab 191 382 DIQLTQSPSSLSASVGDRVTITC RASQGIRNDLG WYQQKPGKAPKRLIY AASSLQS G ADI-19489 Light chain variable region

VPSRFSGSGSGTEFTLTISSLQPEDFATYYC LQHNSYPPT FGQGTKVDIK (“LC”) amino acid sequence

Ab 192 383 EVQLVESGGGLVKPGGSLRLSCAASG FTFSNAWMS WVRQAPGKGLEWVG RIKSK ADI-19490 Heavy chain variable region

TDGGTTDYAAPVKG RFTISRDDSKNTLYLQMNSLKTEDTAVYYC TTDSSSGGMDV (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 192 384 DIVLTQSPLSLPVTPGEPASISC RSSQSLLHSNGYNYLD WYLQKPGQSPQLLIY LGSN ADI-19490 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPLT FGGGTKVDIK (“LC”) amino acid sequence

Ab 193 385 QVQLVQSGPTLVKPTQTLTLICTFSG FSLSTSGVGVG WIRQPPGKALEWLA LIYWD ADI-19491 Heavy chain variable region

DDKRYSPSLKS RLTITKDTSKNQVVLTMTNMDPVDTATYYC AHRRATTVTTGYFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 193 386 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-19491 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGHYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 194 387 QVQLVQSGAEVKKPGESLKISCKGSG YRFTSYWIG WVRQMPGKGLEWMG IIYPG ADI-19492 Heavy chain variable region

DSDTRYSPSFQG QVTISADKSISTAYLQWSSLKASDTAMYYC ARSGSHYAFDL WGQ (“HC”) amino acid sequence

GTMVTVSS

Ab 194 388 NFMLTQPHSVSESPGKTVTISC TRSSGNIASNYVQ WYQQRPGSSPTTVLY EDNQRP ADI-19492 Light chain variable region

S GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDSSNPWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 195 389 QVQLQQWGAGLLKPSETLSLTCAVYG GSFSGYYWS WIRQPPGKGLEWIG EINHSG ADI-19493 Heavy chain variable region

STNYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARLIENTRVGEYYFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 195 390 SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY QDSKRPS GI ADI-19493 Light chain variable region

PERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTVV FGGGTQLTVL (“LC”) amino acid sequence

Ab 196 391 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYVIS WVRQAPGQGLEWMG GIIPIF ADI-19494 Heavy chain variable region

GTTYYAQKFQD RVTITTDESTSTAYMELSSLRSEDTAVYYC ARDLRYRYNAYDGADA (“HC”) amino acid sequence

FDI WGQGTTVTVSS

Ab 196 392 QSALTQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIF EVSNR ADI-19494 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC TSYTKSNSVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 197 393 QVQLQESGPGLVKPSETLSLTCTVSG GSISSYYWS WIRQPPGKGLEWIG YIYTSGST ADI-19495 Heavy chain variable region

NYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARVGSYYDLQH WGQGTLV (“HC”) amino acid sequence

TVSS

Ab 197 394 DIQLTQSPSSVSASVGDRVTITC RASQGISSWLA WYQQKPGKAPKLLIY AASSLQS G ADI-19495 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQANSFPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 198 395 EVQLVESGGGVVQPGGSLRLSCAASG FTFSSYGMH WVRQAPGKGLEWVA FIRYD ADI-19496 Heavy chain variable region

GSNKYYADSVKG RFTISRDNSKSTLYLQMNSLRAEDTAVYYC AKDATFGYSSSWYN (“HC”) amino acid sequence

FDY WGQGTLVTVSS

Ab 198 396 DIQMTQSPDSLAVSLGERATINC KSSQSVLFSSNNKNYLA WYQQKPGQPPKLLIY W ADI-19496 Light chain variable region

ASTRES GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC QQYYSTPT FGQGTKVEIK (“LC”) amino acid sequence

Ab 199 397 QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYYMH WVRQAPGQGLEWMG IINPS ADI-19497 Heavy chain variable region

GGSTSYAQKFQG RVTMTRDTSTSTVYMELSSLRSEDTAVYYC SRGYSYGYDY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 199 398 NFMLTQPHSVSESPGKTVTISC TRSSGSIASNYVQ WYQQRPGSSPTTVIY EDNQRPS ADI-19497 Light chain variable region

GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDSSNWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 200 399 EVQLVESGGGLVQPGGSLRLSCAASG FTVSSNYMS WVRQAPGKGLEWVS VIYSGG ADI-19498 Heavy chain variable region

SAYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AREARISPPQGAFDI W (“HC”) amino acid sequence

GQGTMVTVSS

Ab 200 400 SYVLTQPPSVSVSPGQTARITC SGDALPKQYAY WYQQKPGQAPVLVIY KDSERPS GI ADI-19498 Light chain variable region

PERFSGSSSGTTVTLTISGVQAEDEADYYC QSADSSGTLYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 201 401 EVQLLESGPGLVKPSETLSLTCTVSG GSISSSSYYWG WIRQPPGKGLEWIG SIYYSGS ADI-19499 Heavy chain variable region

TYYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC AVLLYSSSSFDY WGQGTLV (“HC”) amino acid sequence

TVSS

Ab 201 402 NFMLTQPHSVSESPGKTVTISC TRSSGSIASNYVQ WYQQRPGSSPTTVIY EDNQRPS ADI-19499 Light chain variable region

GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDSSNQAV FGGGTQLTVL (“LC”) amino acid sequence

Ab 202 403 EVQLVESGGGLVQPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS YISSSSS ADI-19500 Heavy chain variable region

TIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARGNTVTTFLDY WGQG (“HC”) amino acid sequence

TLVTVSS

Ab 202 404 DIRLTQSPSSFSASTGDRVTITC RASQGISSYLA WYQQKPGKAPKLLIY AASTLQS GV ADI-19500 Light chain variable region

PSRFSGSGSGTDFTLTISCLQSEDFATYYC QQYYSYPPLT FGGGTKVDIK (“LC”) amino acid sequence

Ab 203 405 QVQLVQSGAEVKKPGASVKVSCKASG YAFTNYGVS WVRQAPGQGLEWMG WISV ADI-19501 Heavy chain variable region

YNGNTNYAQKLQG RVTMTTDTSTSTAYMELRSLRSDDTALYYC ARDPPSEGAAGL (“HC”) amino acid sequence

FDY WGQGTLVTISS

Ab 203 406 DIVMTQSPLSLPVTLGQPASFSC RSSQSLVYSDGNTYLS WFQQRPGQSPRRLIY KVS ADI-19501 Light chain variable region

NRDS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQGTHWPCT FGQGTKVEIK (“LC”) amino acid sequence

Ab 204 407 EVQLVESGGGVVQPGGSLRLSCAASG FTFSSDGMH WVRQAPGKGLEWVA FIQYD ADI-19502 Heavy chain variable region

GTNKYYVDSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKDQGFRYSSSWYA (“HC”) amino acid sequence

FDI WGQGTMVTVSS

Ab 204 408 EIVMTQSPDSLAVSLGERATINC KSSQSVLFNSNNKNYLA WYQQKPGQPPKLLIY W ADI-19502 Light chain variable region

ASTRES GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC QQYYSTPT FGQGTRLEIK (“LC”) amino acid sequence

Ab 205 409 QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYYMH WVRQAPGQGLEWMG IINPS ADI-19503 Heavy chain variable region

GGSTSYAQKFQG RVTMTRDTSTSTVYMELSSLRSEDTAVYYC ARDSLVNCSGGSCP (“HC”) amino acid sequence

GGPDY WGQGTLVTVSS

Ab 205 410 SYVLTQPPSVSVSPGQTARITC SGDALPKKYAY WYQQKSGQAPVLVIY EDSKRPS GI ADI-19503 Light chain variable region

PERFSGSSSGTMATLTISGAQVEDEADYYC YSTDSSGNHRV FGGGTKLTVL (“LC”) amino acid sequence

Ab 206 411 QVQLVQSGAEVKKPGESLKISCKGSG YSFTNYWIG WVRQMPGKGLEWMG ITYPG ADI-19505 Heavy chain variable region

DSDTRYSPSFQG QVTISADKSISTAHLQWDSLKASDTAMYYC ARLRCTGSICYDAFD (“HC”) amino acid sequence

I WGQGTTVTVSS

Ab 206 412 SYVLTQPLSVSVALGQTARITC GGNNIGSKNVH WYQQKPGQAPVLVIY RDNNRPS ADI-19505 Light chain variable region

GIPERFSGSNSGNTATLTISRAQAGDEADYYC QVWDSSTGGDV FGAGTKVTVL (“LC”) amino acid sequence

Ab 207 413 QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYGIS WVRQAPGQGLEWMG WISAY ADI-19506 Heavy chain variable region

NGNTNYAQKLQG RVTMTTDTSTSTAYMELRSLRSDDTAVYYC ARVRSVGRFGELL (“HC”) amino acid sequence

YYYYGMDV WGQGTTVTVSS

Ab 207 414 DIRLTQSPLSLPVTPGEPASISC RSSQSLLHSNGYNYLD WYLQKPGQSPQLLIY LGSN ADI-19506 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPWT FGQGTKLEIK (“LC”) amino acid sequence

Ab 208 415 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-19507 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREVLTGDYLGWFDP W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 208 416 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-19507 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSHWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 209 417 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-19509 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ASSRRSLTGDRGGWFD (“HC”) amino acid sequence

P WGQGTLVTVSS

Ab 209 418 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-19509 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 210 419 EVQLVESGGGLVKPGGSLRLSCAASG FSLSSYYMN WVRQAPGKGLEWVS SISSSST ADI-19510 Heavy chain variable region

YINYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARGGSITIFGVVFDS WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 210 420 SYELTQPPSVSGAPGQRVTISC TGTSSNIGAGYDVH WYQQLPGTAPKLLIY VNSNRP ADI-19510 Light chain variable region

S GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGGV FGTGTKVTVL (“LC”) amino acid sequence

Ab 211 421 QITLKESGPTLVKPTQTLTLTCTFSG FSLSTSGVGVG WIRQPPGKALEWLA LIYWDD ADI-19511 Heavy chain variable region

DKRYSPSLKS RLTITKDTSKNQVVLTMTNMDPVDTATYYC AHSVYYDFWSGYYVPN (“HC”) amino acid sequence

YFDY WGQGTLVTVSS

Ab 211 422 DIQMTQSPSSLSASVGDRVTITC RASQGIRNDLG WYQQKPGKAPKRLIY AASSLQS ADI-19511 Light chain variable region

GVPSRFSGSGSGTEFTLTISSLQPEDFATYYC LQHNSYPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 212 423 EVQLLESGAEVKKPGASVKVSCKTSG YTFSNYGVS WVRQAPGQGLEWLG WISAYN ADI-20959 Heavy chain variable region

GNTNYAQKLQG RVTMTTDSSTSTAYMEVRSLRSDDTAVYYC ARDVAPVAASLFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 212 424 DIRLTQSPLSLPVTLGQPASISC RSSQSLEFTDGNTYLS WFQQRPGQSPRRLIY KVSN ADI-20959 Light chain variable region

RDS GVPDRFSGSGSGTDFTLKINRVEAEDVGVYYC MQGIHWPPT FGPGTKVEIK (“LC”) amino acid sequence

Ab 213 425 QVQLQQWGAGVLKPSETLSLTCAVNG RSLSGHYWS WIRQTPGKGLEWIG EINNS ADI-20960 Heavy chain variable region

GGTHYSPSLKS RVIISGDTAKNQLSLKLSSVTAADTAVYYC AKGSAEWYFDL WGRGT (“HC”) amino acid sequence

LVTVSS

Ab 213 426 DIRVTQSPSTLSASVGDRVTITC RASQSVSTWLA WYQQKPGKPPSLLIF KASTLES GV ADI-20960 Light chain variable region

PSRFSGSGSGTEFTLTISSLQPDDFATYYC QQYNTYSPWT FGPGTKVEIK (“LC”) amino acid sequence

Ab 214 427 QVQLVESGGGLVKPGGSLRLSCAASG FKFSSYYMH WVRQAPGKGLEWVS SVSGG ADI-20961 Heavy chain variable region

STYTSYADSVKG RFTISRDNAKHSLFLQLNSLRAEDTAVYHC VRGDYHPSGTSLNWF (“HC”) amino acid sequence

DP WGQGTLVTVSS

Ab 214 428 QPGLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYKQLPGTVPKLLIY ANNNR ADI-20961 Light chain variable region

PS GVPDRFSGSESGTSASLAITGLQAEDEADYYC QSYDSSLNAYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 215 429 QVQLVQSGAEVKKPGASVKVSCKASG YTFSHYGLS WVRQAPGQGLEWMG WISA ADI-20962 Heavy chain variable region

YNHNTNYAQKFQG RVTITTDTSTSTAYLEMRSLRSDDTAVYYC AREPPSDTAAGTG (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 215 430 DIVMTQSPLSLSVTLGQPASISC RSSQSLVYSDGNTYLT WFQQRPGQSPRRLIY KVS ADI-20962 Light chain variable region

NRDS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQGTQWPRT FGQGTKVDIK (“LC”) amino acid sequence

Ab 216 431 EVQLVESGGGLAKPGGSLRLSCAASG FTFSHYNMN WVRQAPGKGLEWVS SISSTG ADI-20963 Heavy chain variable region

FHIYYADSVKG RFVISRDNAENSLHLQMNSLRADDTGLYYC VRAEYYYGSGSAGHY (“HC”) amino acid sequence

FDS WGQGTLVTVSS

Ab 216 432 SYVLTQPPSVSVAPGHTAKITC GGSIIGTKSVH WYQQKPGQAPVLVVY DDSDRPS GI ADI-20963 Light chain variable region

PERLSGSRSGNTATLTITRVEAGDEADYYC QVWDSSSEHAGV FGGGTKLTVL (“LC”) amino acid sequence

Ab 217 433 QVQLVQSGAEVKKPGASVKVSCKASG YTFTHYGIS WVRQAPGQGLEWMG WISAY ADI-20964 Heavy chain variable region

NGNTNYAQKLQG RVTMTTDTSTSTAYMEVRSLRYDDTAVYYC ARDVPVEAATSPE (“HC”) amino acid sequence

F WGQGTLVTVSS

Ab 217 434 DIVMTQTPLSLPVTLGQPASISC RSSQSLVYSDGNTYLS WFQQRPGQSPRRLIY KVS ADI-20964 Light chain variable region

NRDS GVPNRFSGSGSGTDFTLKISRVEAEDVGVYYC VQNTHWPAYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 218 435 QVQLVQSGAEVKKPGASVKVSCKASG YNFTNYGIS WVRQAPGQGLEWMG WIST ADI-20965 Heavy chain variable region

SNGNTHYAQKSQG RITLTTDTSTNTAYMEVRSLRSDDTAVYYC AREGPESTYDWY (“HC”) amino acid sequence

HFDS WGQGTLVTVSS

Ab 218 436 QSVVTQPPSVSVAPGQTAKITCG GNNIGSKTVH WYQLKAGQAPVLVVY DDSDRPS ADI-20965 Light chain variable region

GIPERFSGSNSGNTATLTIRRVEAGDEADYFC QVWESASDHWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 219 437 EVQLLESGGGLGKPGGSLRLSCAASG FKLSSYYMH WVRQAPGKGPEWVS SISASSS ADI-20966 Heavy chain variable region

YINYADSVRG RFTVSRDNAKNSLFLQMNSLRVDDTAIYYC ARGAPLTNFGMVLDS (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 219 438 QSVLTQPPSVSGAPGQRVTISC TGSGSNIGAGYDVH WYQQVPGRVPKLLIY ANNN ADI-20966 Light chain variable region

RPS GVPDRFSGSKSGTSASLAITGLQADDEADYYC QSYDRSLNVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 220 439 EVQLLESGGGVVQPGRSVRLSCAASG FSFSSYALH WVRQAPGKGLEWVG VIWYEE ADI-20967 Heavy chain variable region

SNKYYADPVKG RFTISRDNSKNTLYLQMNSLRDEDTAVYYC ARKGVATAGLDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 220 440 EIVLTQSPLSLPVTPGEPASISC RSSQSLLNSNGYNYLD WYLQKPGQSPQLLIY LGSNR ADI-20967 Light chain variable region

AS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPQT FGPGTKVDIK (“LC”) amino acid sequence

Ab 221 441 QVQLQQWGAGLLKPSETLSLTCAMYG GSFSDDYWS WIRQPPGKGLEWIG EVNH ADI-20968 Heavy chain variable region

GGSTNYNTSLKS RVTISADTSKKQFSLKLRSVTAADTAVYFC ARGWRYCNATTCYSK (“HC”) amino acid sequence

AFDI WGQGTMVTVSS

Ab 221 442 DIQMTQSPSSLSASVGDRVTITC QASQDIDIYLI WYQQKPGRAPKLLIY DASNLKT GV ADI-20968 Light chain variable region

PSRFSGSGSGTEFTFTINNLQPEDFATYYC QQFHDLPLT FGGGTKLEIK (“LC”) amino acid sequence

Ab 222 443 EVQLVESGGGLVKPGGSLRLSCAASG FKFSSYTMN WVRQAPGKGLEWVS SVSASS ADI-20969 Heavy chain variable region

SYIFYADSVQG RFIISRDNAQNSLYLQMNSLRADDTAVYYC ARDQYGPGHYYNPA (“HC”) amino acid sequence

WFDP WGQGTLVTVSS

Ab 222 444 QPVLTQPPSVSGAPGQRVTISC TGTSSNIGAGYDVH WYKQLPGTAPKVLIY GNTNR ADI-20969 Light chain variable region

PS GIPDRFSGSKSGTSASLAITGLKAEDEADYY CQSYDRSGSKV FGTGTKLTVL (“LC”) amino acid sequence

Ab 223 445 EVQLLESGGGLVKPGGSLRLSCAVSG FSFSNAWMS WVRQAPGKGLEWVG RIRSKT ADI-20970 Heavy chain variable region

DGGTTDYAAPVKG RFTISRDDSKNTLYLQMNSLKTEDTAVYYC TTAPRYSTSWYPG (“HC”) amino acid sequence

YYYYYYMDV WGKGTTVTVSS

Ab 223 446 DIQMTQSPSSLSASVGDRVTITC QASQDINFYLN WYQQKPGKAPKLLIY DASNLET G ADI-20970 Light chain variable region

VPSRFSGSVSGTDFTFTISSLQPEDFATYYC QQYDDLPA FGGGTKVEIK (“LC”) amino acid sequence

Ab 224 447 EVQLVESGGGLVKPGESLRLSCAASG FTFSDYSMT WIRQAPGKGLLEWIA YINSQS ADI-20971 Heavy chain variable region

NYMDYADSVKG RFTISRDNAKNSLYLQMNGLRADDTAVYFC ARDRRTFVAATLG (“HC”) amino acid sequence

WFDPWGQGTLVTVSS

Ab 224 448 ETTLTQSPATLSVSPGERATLSC RASQSVSNNVA WYQQKPGQAPRVLIY AASTRAT ADI-20971 Light chain variable region

GIPARFSGSESGTEFTLTISSLQSEDFAVYYC QQYNNWPRT FGQGTKLEIK (“LC”) amino acid sequence

Ab 225 449 QVQLQQWGAGLLRPSETLSLTCAVSG GSFSGHYWS WIRQPPGKGLEWIG GINHS ADI-20972 Heavy chain variable region

GNTNYSPSLRS RVTMSVDTSRNQFSLMLRSVTAADTAVYFC ARNVPNLYGDYPRW (“HC”) amino acid sequence

FDP WGQGTLVTVSS

Ab 225 450 QSVLTQPASVSGSPGQSITISC TGTSSDVGGFNYVS WYQHHPGKAPKLMIY DVNN ADI-20972 Light chain variable region

RPS GASNRFSGSKSGNTASLTISGLQAEDEADYYC SSYRSSDTLYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 226 451 EVQLLESGGGLVKPAGSLRLSCAASG FSFSSYYMN WIRQAPGKGLEWVS DISGGSS ADI-20973 Heavy chain variable region

YTNYADSVKG RFTVSRDNAKNSVYLQMNSLRGEDTAVYYC ARGASTAATYTPTFD (“HC”) amino acid sequence

Y WGQGILVTVSS

Ab 226 452 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLMF GNNN ADI-20973 Light chain variable region

RPS GVPDRFSGSKSGTSASLAITGLRPEDEADYYC QSYDRRLTVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 227 453 EVQLVESGGGLVKPGGSLRLSCAASG FSFSSYQIN WVRQAPGKGLEWVS SISGGSS ADI-20974 Heavy chain variable region

YTDYADSIKG RFTISRDNAKKSAFLQMKSLRADDTAVYYC ARALMATAGGLAFDI W (“HC”) amino acid sequence

GQGTMVTVSS

Ab 227 454 QPVLTQPPSVSGAPGQRVTISC TGSGSNIGAGYDVH WYQQVPGTAPKLLIL RNTNR ADI-20974 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDRSLSVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 228 455 QVQLVESGTHVKKPGASVKVSCEASD DTFNNKGIV WVRQAPGQGLEWMG WIRP ADI-20975 Heavy chain variable region

NNGNTKYAQKFQG RVTMTTDASTNTAYMELRSLRSGDTAVYYC AREQFKWNDFY (“HC”) amino acid sequence

FDY WGQGILVTVSS

Ab 228 456 SYELMQPPSVSVAPGQTATITC GGSNIGSETVH WYQQKPGQAPVLVVH DDTDRPS ADI-20975 Light chain variable region

GIPERFSGSNSGNTATLTISGVEAGDEADFYC QVRDSRTDDVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 229 457 QVQLVESGGDLVQKGGSLRLSCAASG FTFDNYAMT WIRQAPGQGLEWVS TVSGF ADI-20976 Heavy chain variable region

VLGTGYTTYYADSVKG RFTISRDSSKNTVYLQLNSLRAEDTAVYYC AKCAATRNECL (“HC”) amino acid sequence

WDYLQQ WGQGTTVTVSS

Ab 229 458 EIVMTQSPSSLSASVGDRVTITC RASQSVSIYLN WYQQKGGKAPKLLIY GASALQR G ADI-20976 Light chain variable region

VPSRFSGSGSGTDFTLTITSLQPEDFATYFC HQSYSAPQT FGQGTKVDIK (“LC”) amino acid sequence

Ab 230 459 EVQLVESGGGLVQPGGSLRLSCAASG FTFTNYAMS WVRQAPGKGLEWVS GISGS ADI-20977 Heavy chain variable region

GGSTYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKDQGYAVVVADA (“HC”) amino acid sequence

TRNLPPRRYGMDV WGQGTTVTVSS

Ab 230 460 EIVLTQSPGTLSLSPGERATLSC RASHSVSSSYLA WYQQKPGQAPRLLIY GASSRAT GI ADI-20977 Light chain variable region

PDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPLT FGGGTKVDIK (“LC”) amino acid sequence

Ab 231 461 EVQLVESGAEVKKPGASVKVSCKASG YTFGNYGIS WVRQAPGQGLEWMG WISAY ADI-20978 Heavy chain variable region

NGNSNYAQKFQG RVTMTTDTSASTAYMEVRSLRSDDTAVYYC ARDVPVTAARLLD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 231 462 DIVLTQTPLSLPVTLGQPASISC RSSQSLVYSDGNTYLS WFQQRPGQSPRRLIY KVSN ADI-20978 Light chain variable region

RDS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQATDWLGYT FGQGTKLEIK (“LC”) amino acid sequence

Ab 232 463 EVQLQESGPGLVKPSETLSLTCTVSG GSLRSYYWS WIRQPPGKGLEWIG NIYYGGST ADI-20979 Heavy chain variable region

NYNSSLKG RVTISIDTSKNQFSLRLSSVTAADTAVYYC ARDGLFPMGEWDY WGQGI (“HC”) amino acid sequence

LVTVSS

Ab 232 464 QSALTQPASVSGSPGQSITISC TGTSNDVGDYNYVS WYQQHPGEAPKLMIY EVTNR ADI-20979 Light chain variable region

PS GVSDRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSTSVV FGGGTQLTVL (“LC”) amino acid sequence

Ab 233 465 QVQLQESGPGLVKPSQTLSLTCSVSG GSVSSGDYYWT WIRQPAGKGLEWIG RIYNS ADI-20980 Heavy chain variable region

GGTDYSPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARGRGYYESP WGQGTL (“HC”) amino acid sequence

VTVSS

Ab 233 466 EIVLTQSPATLSLSPGERATLSC RASQSVGIYIG WYQQKPGQAPRLLMY DASNRAT G ADI-20980 Light chain variable region

IPDRFSGSGSGTDFSLTISSLEPEDFAVYYC QLRSKWLT FGPGTKVEIK (“LC”) amino acid sequence

Ab 234 467 QVQLQESGPRLVKPSETLSLICTVSG DSISSRNYFWA WIRQPPGKGLEWIG TIYYSG ADI-20981 Heavy chain variable region

NTYSNPSLKS RVTISVDTSKKQFSLNLSSVTAADTAVYYC ARGAYGGDAFDI WGQG (“HC”) amino acid sequence

TVVTVSS

Ab 234 468 DIRVTQSPSSVSASVGDRVTITC RASQGIGTWLA WYQQKPGKAPHLLIY AASRLQS ADI-20981 Light chain variable region

GVPSRFSGSGSGTDFTLSISSLHPEDFATYYC QQAYAFPRT FGQGTKVEIK (“LC”) amino acid sequence

Ab 235 469 EVQLVESGPGLVKPSQTLSLICSVSG VSISRGSYYWS WIRQPAGGGLEWIG RIYTSG ADI-20982 Heavy chain variable region

VTRYNPSLES RVTISLDSSQNQFFLRLSSVTAADTAVYYC ATRESASYSSGPDAFDI W (“HC”) amino acid sequence

GQGTTVTVSS

Ab 235 470 DIQMTQSPSTLSASVGDRVIITC RASQSVNSWLA WYQQKPGKAPKLLIY QASSLES G ADI-20982 Light chain variable region

VPSRFSGSGSGTEFTLTINSLQPDDFATYYC QQYKTFSRP FGQGTKVEIK (“LC”) amino acid sequence

Ab 236 471 EVQLVESGGALVQPGGSLRLSCSASG FTFSSYAMH WVRQAPGKGLEYVS AINNFG ADI-20983 Heavy chain variable region

DKTYYTDSVEG RFTISRDNSKKTLYLQMSSLRPEDTAVYYC VKDRGYCSSPSCYAVPY (“HC”) amino acid sequence

YYFYGMDV WGQGTTVTVSS

Ab 236 472 EIVMTQSPSSLSASVGDRVTITC QASQGISNYLH WYQQKPGKAPKLLIY DASNLEA G ADI-20983 Light chain variable region

VPSRFSGSGAGTDFTFTISSLQPEDVATYYC QHYNNLPFT FGPGTKVDIK (“LC”) amino acid sequence

Ab 237 473 EVQLLETGAEVKKPGASVKVSCHVSG YGLTDLSMH WVRQAPGKRLQWMG SFDP ADI-20984 Heavy chain variable region

QYGETIDTQNFQG RVTMTVDTSTATLYMQLSGLRSEDTAMYYC ATPQSTGALDN (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 237 474 DIRVTQSPSSLSASVGDRVTITC RASQSISSYLS WYQQKPGKAPRLVIF AASNLQS GV ADI-20984 Light chain variable region

PSRFSGTGSSRFSDSGSWTDFTLTISSLQPEDFAIYYC QQTYITPFT FGQGTKVDIK (“LC”) amino acid sequence

Ab 238 475 EVQLVESGGGLVQPGGSLRLSCVASG FTFSNYWMN WVRQAPGKGLEWVA NIKE ADI-20986 Heavy chain variable region

DGSEIKYVDSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARTEDSSSWFVAID (“HC”) amino acid sequence

YYNYMDV WGKGTTVTVSS

Ab 238 476 DIQVTQSPGTLSLSPGERATLSC RASQTVSSSYLA WYQQKPGQAPRLLFY GASSRAT ADI-20986 Light chain variable region

DIPDRFSASGSGTDFTLTIHRLEPEDFAVYYC QLYGRSPPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 239 477 QVQLVQSGGGVVHPGRSLRLSCAASG FSFSDYGMH WVRQAPGKGLEWVA VIWY ADI-20987 Heavy chain variable region

DGINKYYADSVKG RFAISRDNSKNTLYLQMNSLRAGDTAVYYC ARGGIAAAQRYFD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 239 478 ETTLIQSPGILSLSPGERATLSC RASQTVSSSNLA WYQQKPGQAPRLLIY GASSRAT ADI-20987 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQSGTS FGQGTKVDIK (“LC”) amino acid sequence

Ab 240 479 EVQLVESGGEVKKPGASVKVSCKTSG YPFSNYGIS WMRLAPGQGLEWMG WISSY ADI-20988 Heavy chain variable region

NGNTYYTKKFQG RVSMTTDTSTSTAYMELRSLRSDDTAVYYC ARDVPVIAAHTFEY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 240 480 ETTLTQSPLSLPVTLGQPASISC RSSESLVYSDGNTYLS WFQQRPGQSPRRIIY KVSNR ADI-20988 Light chain variable region

DS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQATHWPRDT FGQGTKVDIK (“LC”) amino acid sequence

Ab 241 481 EVQLLESGPGLVKPSGTLSLTCAVSG GSIINSNWWS WVRQSPGKGLEWIG DIYHSG ADI-20989 Heavy chain variable region

STTYNPSLKS RVTISVDRSKNQYSLRLTSVTAADTAVYYC AKIGPDNRSGPDYYYFM (“HC”) amino acid sequence

DV WGKGTTVTVSS

Ab 241 482 EIVLTQSPSSLPASVGDRVTISC RASQSISNYVY WYQQKPGKAPKLLIY AASSLQS GV ADI-20989 Light chain variable region

PSRFSGSGSGTDFTLSISSLQFEDFATYFC QQSYSTPPT FGQGTKLEIK (“LC”) amino acid sequence

Ab 242 483 EVQLVESGGGVVQPGRSLRLSCSASG FPFHSYAMH WVRQAPGKGLEWVA GIWYE ADI-20990 Heavy chain variable region

GSSESYADSVKG RLTISRDNSRNTLYLQMNSLRVEDTAVYYC ARRGSFSGFDS WGQ (“HC”) amino acid sequence

GSLVTVSS

Ab 242 484 DIVMTQSPLSLPVTPGEPASISC RSSQSLLHSNGYNYLD WYLQKPGQSPQLLIS LGSN ADI-20990 Light chain variable region

RAS GVPDRFSGSVAGTDFTLKISRVEAEDVGVYYC MQSSQTPYT FGQGTKVDIK (“LC”) amino acid sequence

Ab 243 485 EVQLVESGGNLVKPGGSLRLSCAASG FTFSGYYMS WIRQAPGKGLEWIS DISGGSS ADI-20991 Heavy chain variable region

YTNYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAMYYC ARVEYDTTGPFHFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 243 486 QPVLTQPPSVSGAPGQRVTISCT GSSSNIGAGYDVH WYQQLPGTAPKLLIY GNNNR ADI-20991 Light chain variable region

PS GVPDRLSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYV FGIGTKVTVL (“LC”) amino acid sequence

Ab 244 487 EVQLVESGGGLVQPGGSLRLSCVVSG FTFKSYWMT WVRQAPGKGLEWVA NIKED ADI-20992 Heavy chain variable region

GSEKYYVDSVKG RFTISRDNARNSLFLQMNSLRADDTAVYYC ARNLEVSNEFYVVT (“HC”) amino acid sequence

DNYYLMDV WGQGTTVTVSS

Ab 244 488 DIQLTQSPSSLSASVGDRVTITC RASQSISFFLN WYRQKPGKAPKLLIY AASTLQS GVP ADI-20992 Light chain variable region

SRFSGSGSGTDFTLTISSLQPEDFASYYC QQSYSTPHT FGQGTKVEIK (“LC”) amino acid sequence

Ab 245 489 EVQLVESGGGVVQPGRSLRLICAASG FPFSSYAMH WVRQAPGKGLEWVA VTWY ADI-20993 Heavy chain variable region

DGPNRDYADSVKG RFTVSRDNSKNTLYLQMTSLRADDTAVYYC ARRGSWGSFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 245 490 DIVMTQSPLSLSATPGEPASISC RPSQSLLHSNGYNYLE WYLQKPGQSPQLLIY LGSN ADI-20993 Light chain variable region

RAS GVPDRFSGGGSGTDFTLRISRVEADDVGVYYC MQASQTPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 246 491 QVQLVQSGAEVKKPGASVKVSCKASG YTFSSNVIG WVRQAPGQGLEWMG WIST ADI-20994 Heavy chain variable region

NNGNTKYGQKFQG RVIMITDPSTSTAYMELRSLRSDDTAFYYC ARESLGMGGFYF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 246 492 QPVLTQPPSVSVAPGQTARITC GGDNIGSKSVH WYQQKPGQAPVLVVY DDSDRPS ADI-20994 Light chain variable region

GIPERFSGSNSGNTASLTISRVEAGDEADYCC QVWDSGSDLWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 247 493 QVQLVESGPALVKPTQTLTLTCTFSG FSLTTRGMCVS WIRQPPGKALEWLA RIDWD ADI-20996 Heavy chain variable region

DDKYYSTSLKT RLTISKDTSKNQVVLTMTNMDPVDTATYYC ARASTLTTAGYYLHYK (“HC”) amino acid sequence

DV WGNGTTVTVSS

Ab 247 494 DIRMTQSPSSLSASVGDRVTITC RASQSIGTYLN WFQQKPGKAPNLLIY AASILHS GV ADI-20996 Light chain variable region

PSRFSGSGSGTDFTLTIRTLQPEDFATYYC QQSYPTVT FGQGTKVEIK (“LC”) amino acid sequence

Ab 248 495 EVQLVESGGGVVQPGRSLRLSCAASG FPFNSYGMH WVRQAPGKGLEWLA VIYFD ADI-20997 Heavy chain variable region

ESTAYYADSVKG RFTISRDNSKSTLYLQMNSLRAADTAIYYC TTTVMIPYGGVF WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 248 496 EIVMTQSPGTLSLSPGDRATLSC RASQSVGSTHFA WYQQKPGQAPRLLIY AASIRAT ADI-20997 Light chain variable region

GIPDRFSGGGSGTDFTLTISRLAPEDFAVYYC QQYGSTPIT FGQGTRLEIK (“LC”) amino acid sequence

Ab 249 497 QVQLVQSGGGVVQPGRSLRLSCAASG FTLSTYGMH WVRQAPGKGLEWVA VIYYD ADI-20998 Heavy chain variable region

ESNKFYADSVQG RFTISRDDSKNTLFLQMNSLRAEDTAVYYC ARESRPRGYSYSDFD (“HC”) amino acid sequence

S WGQGTLVTVSS

Ab 249 498 QPGLTQPRSVSGSPGQSVTISC TGTSSDVGTFNYVS WYQQHPGKAPKLMIY DVNQ ADI-20998 Light chain variable region

RPS GVPDRFSGSKSGNTASLTISGLQAEDEADYYC CAYAGYYS FGGGTKLTVL (“LC”) amino acid sequence

Ab 250 499 QVQLQESGPVLVKPSETLSLICTVSG GSITSSAYYWG WIRQPPGKGLEWIG SVSYSG ADI-20999 Heavy chain variable region

TTSYTPSLKS RVTISGDASKEQFSLNLRSVTAADTAVYYC ARQTKAFGRRDYGMDV (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 250 500 QPVLTQPPSVSAAPGQKVTISC SGSNSNIGSNFVS WYQQLPGTAPKLLIY ENNKRPS ADI-20999 Light chain variable region

GIPDRFSGSKSGPSATLGITGLQTEDEADYYC GTWDTGLSAHWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 251 501 EVQLVESGPVLVKPRGTLTLTCTVSG FSLSDARMGVS WIRQPPGKALEWLA HIFWD ADI-21000 Heavy chain variable region

DEKSYSTSLKN RLTISKDTSRGQVVLRMTNMDPVDTGTYFC ARVNTYHSGGYYLYY (“HC”) amino acid sequence

FDV WGQGTLVTVSS

Ab 251 502 EIVLTQSPSSLSASVGDRVTITC RASQIIASYLN WYQQKPGQAPKLLIY AASSLQS GVP ADI-21000 Light chain variable region

SRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTRMYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 252 503 EVQLVESGPGLVKPSETLSLTCTVSG GSISDIDYYWG WIRQPPGKGLEWIG SIYYSGS ADI-21001 Heavy chain variable region

TYYNPSLES RVTISVDTSKNQFSLKLRSVSAADTALYHC ARHGPPWVVTAIRGHAFD (“HC”) amino acid sequence

V WGQGTTVTVSS

Ab 252 504 DIRVTQSPDSLAVSLGERATINC KSSQSILYSSNNKNYLA WYQQKPGQPPKLLIY WA ADI-21001 Light chain variable region

STRES GVPDRFSGSGSGTDFILTISSLQAEDVAVYYC QEYYSYPPMYT FGQGTKVDI (“LC”) amino acid sequence

K

Ab 253 505 QVQLVESGPGLVKPSGTLSLTCAVSG DSINSGNWWN WVRQAPGKGLEWI GEIYH ADI-21002 Heavy chain variable region

RGTSNYNPSLKS RVTISVDQSKNQFSLKVTSLTAADTAIYYC ARARGYSSGPSYYYYL (“HC”) amino acid sequence

DV WGKGTLVTVSS

Ab 253 506 EIVMTQSPSSLSASVGDRVTISC RASQSISTYLN WYQQKPGKAPKVIIY GASNLQS GV ADI-21002 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QKSFNPCV FGQGTKVDIK (“LC”) amino acid sequence

Ab 254 507 QVQLQQWGAGLLKPSETLSLSCAVSG GSFSGYYWT WIRQPPGKGLEWIG EINHSG ADI-21003 Heavy chain variable region

STNYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARARYFDYLAHWSFDL W (“HC”) amino acid sequence

GRGTLVTVSS

Ab 254 508 GIQMTQSPLSLPVTPGEPASISC RSSQSLLHSNGYKYLD WYLQKPGQSPQLLIY LGSD ADI-21003 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPWT FGQGTKLEIK (“LC”) amino acid sequence

Ab 255 509 QVQLQESGGGVVQPGRSLTLSCAASG FTFSSYGMH WVRQAPGKGLDWVA EIWY ADI-21004 Heavy chain variable region

DGSNKYYVDSVKG RFTISRDNSKNTLYLQMKSLRAEDTAIYYC ARDGGYESPFFDK (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 255 510 EIVMTQSPDSLGVSLGERATINC KSSQSLYTSNHENSLA WYQQKPGQPPRLLIY WA ADI-21004 Light chain variable region

STREL GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC QQYHTTPLTF GPGTKVEIK (“LC”) amino acid sequence

Ab 256 511 EVQLVESGGAVVQPGGSLRLSCVASG LAFDEYTMH WVRQSSAKGLEWIS LISWNG ADI-21005 Heavy chain variable region

GITYYADSVKG RFTISRDNSKNSLYLQMNSLRTEDTATYFC ARLGYGSGSDYGDDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 256 512 ETTLTQSPGTLSLSPGERATLSC RASQSVSNNYLA WYQQKPGQAPRLLIH GASTRVT ADI-21005 Light chain variable region

GIPARFSGSGSGTDFTLTISRLEPEDFAVYYC HQYHSSPRT FGQGTKVDIK (“LC”) amino acid sequence

Ab 257 513 QVTLKESGPTLVKPTQTLTLTCTFSG FSLSISGVGVG WIRQPPGKALEWLA VMYWD ADI-21006 Heavy chain variable region

DDKRYSPSLKT RLTITKDTSKNQVVLTMTNMAPVDTAIYYC AHLWFGEAAFDP WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 257 514 EIVLTQSPLSLPVTLRQTASISC RSGQSLLYSDGNTYLN WFQQRPGQSPRRLIS IVSKR ADI-21006 Light chain variable region

DS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQGTHWPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 258 515 QVQLVQSGADVKKPGASVKVSCKSSG YTFSNHSMH WVRQAPGQGLEWMG RIHP ADI-21007 Heavy chain variable region

SSGTTTYAQKFQG RVTMTRDTSTSTVYMEVSSLRSEDTAVYYC ARSPFFDFDF WG (“HC”) amino acid sequence

QGTMVTVSS

Ab 258 516 SYVLTQPHSVSESPGKTVTISC TRSSGSIASNYVQ WYQQRPGSAPTSVIY EDNQRPS ADI-21007 Light chain variable region

GVPDRFSGSIDSTSNSASLTISGLKTEDEADYYC QSYYSSGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 259 517 QVQLQESGAGLLKPSETLSLTCTVYG GTFSGYHWN WIRQPPGKGLEWIG EINHRE ADI-21008 Heavy chain variable region

NTDYNASLES RVTISVDTSKRQFSLKMNSVTVADTAVYYC ARGIQVLTNLGTEVRVH (“HC”) amino acid sequence

QFLDL WGRGTLVTVSS

Ab 259 518 DIVLTQTPATLSLSPGERATLSC RASQSVSTYLA WYQQKPGQAPRLLIY DASNRAA GI ADI-21008 Light chain variable region

PARFSGSGSGTDFTLTISSLEPEDFAVYYC QQRTNWLPLT FGGGTKVDIK (“LC”) amino acid sequence

Ab 260 519 QVQLVQSGAEMKTPGASVKVSCKASG YSFSNYGFT WVRQAPGQGLEWMG WIS ADI-21009 Heavy chain variable region

GYSAKTNYAQDLQG RVTMTIDTSTSTSYMELRSLRSDDTAVYYC ARDPLGYFGSGT (“HC”) amino acid sequence

YRGGAFDF WGQGTTVTVSS

Ab 260 520 QSALTQPASVSGSPGQSITLSC TGTNNDVGSYHLVS WYQQYPGKAPKLVIY EVTKR ADI-21009 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQPEDEADYYC CSYAGDRRI FGGGTKVTVL (“LC”) amino acid sequence

Ab 261 521 EVQLVESGGGVVQPGRSLRLSCAASG FSFSTYGMH WVRQAPGKGLEWVG VIWY ADI-21010 Heavy chain variable region

DETTKYYADSVKG RFSISRDNSKNMVYVQMNSLRADDTALYYC AREVWGGVFDI (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 261 522 DIQMTQSPATLSASVGDRVTITC RASQNIVTWLA WYQQKPGKAPNLLIY KASSLES ADI-21010 Light chain variable region

GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QHYNSYSGA FGQGTKVDIK (“LC”) amino acid sequence

Ab 262 523 QVQLQESGPGLVKPSETLSLSCTASG DSISDYYWS WIRQPPGKGLEWIG FVSDTWG ADI-21011 Heavy chain variable region

TNYSPSLTS RVAISLDTSRSQVSLRLRSVTAADTAVYYC VRTHLYDRGGYYLYYFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 262 524 DIRMTQSPPSLSASVGDRVTITC RASQRIASYLN WYQQKPDTAPKLLIY AASNLQT G ADI-21011 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPYT FGQGTKLEIK (“LC”) amino acid sequence

Ab 263 525 QVQLVQSGPAVVKPTQTLTLTCSFSG FSLSTSRMSVS WIRQPPGKALEWLA RIDWD ADI-21012 Heavy chain variable region

GDKYYSTSLKS RLTISKDTSKNQVVLTMTNMDPVDTATYYC ARGSYYVSSGYYLNYF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 263 526 DIRMTQSPSSLSASVGDRVTITC RTSQTIASYLN WYQQKPGKAPNLLIY AASILQT GV ADI-21012 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYGTPQT FGQGTKVEIK (“LC”) amino acid sequence

Ab 264 527 QVQLQESGPGVVKPSETLSLTCTVSG GSISNTHSYWG WIRQSPGKGLEWIG SIYYT ADI-21013 Heavy chain variable region

GSTYYNPSFRS RVTLSVDTSKNQFSLKLSSVTAADTAVYYC AAPDYFVLTDYKSTFDY (“HC”) amino acid sequence

WGRGALVTVSS

Ab 264 528 DIVMTQSPGTLSLSPGGRATLSC RASQSVGSSSLA WYQQKPGQAPRLLIY GASSRA ADI-21013 Light chain variable region

A GIPDRFSGSGSGTDFTLTINRLEPEDFAMYYC QQYGSSPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 265 529 QVQLQESGPGLVKPSETLSLICTVSG GSISNYYWS WIRQPPGKGLEWIG YVWFGTT ADI-21014 Heavy chain variable region

KYNPSLKN RVTISVDTGKNQVSLKVNSVTAADTAIYYC ARDSSIWYRGAFEI WGQG (“HC”) amino acid sequence

TTVTVSS

Ab 265 530 DIRLTQSPSSLSASVGDRVTITC QASQDISNHLN WYQQRPGKAPELLIY DASTLET G ADI-21014 Light chain variable region

GPSRFSGSGSGTDFTLTISSLQPEDFADYYC QQYDNLPVT FGGGTKVDIK (“LC”) amino acid sequence

Ab 266 531 QVQLVQSGAEVKKPGASVRVSCKVPG NTLSDLSMH WVRHTPGEGLEWMG SFDP ADI-21015 Heavy chain variable region

EYGETIPAQRFQG RVTMTEDTSTDTAYMELTSLRFEDTAVYYC AAPHASGALQH W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 266 532 DIVMTQSPSSLSASVGDRVTITC RASQIISAYLN WYQQKAGKAPKLLIY AASSLQS GV ADI-21015 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQTYITPFT FGQGTKLEIK (“LC”) amino acid sequence

Ab 267 533 QVQLVESGTEVKKPGASVKVSCKASG YTFTNYGIT WVRQAPGQGLEWMG CISGY ADI-21017 Heavy chain variable region

NGNTNYAQNLQG RVTMTTDTSTNTAYMELRSLISDDTAVYYC ARDTGLTAAALLD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 267 534 DIVLTQSPLSLPVTLGQPASISC RSSQSLVYSDGNTYLS WFQQRPGQSPRRLIY KVSN ADI-21017 Light chain variable region

RDS GVPDRFGGSGSGTYFTLKISRVEAEDVGIYYC MQAIHWPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 268 535 EVQLLESGGGLVKPGGSLRLSCAGSG FTLSSYGMN WVRQAPGQGLEWIS SISSSSS ADI-21018 Heavy chain variable region

YINYADSVKG RFTISRDNAQNSLYLQLNSLRAEDTAVYYC ARGGLGYDYGLGSYTYA (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 268 536 QSVVTQPPSVSGAPGQRVTISC TGSSSNTGAGYDIH WYQQLPGTGPKLLIY GNKNR ADI-21018 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGWV FGGGTKVTVL (“LC”) amino acid sequence

Ab 269 537 EVQLLESGGGLVRPGGSLRLSCAVSG FTFSGNALT WIRRAPGKGLEWVS TIGDSGG ADI-21019 Heavy chain variable region

GSYYADSVKG RFTISRDNSKSTLYLQMNSLTAEDTAVYYC ARDPYGDYRDYYGIDV (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 269 538 EIVMTQSPLSLPVTPGEPASISC RSSQSLRHSNGYNYVD WYLQKPGQSPQLLIY LGS ADI-21019 Light chain variable region

NRAS GVPDRFRGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPLT FGQGTKVEIK (“LC”) amino acid sequence

Ab 270 539 QVQLQQWGAGLLKPSETLSLTCAVHG GSFSGFYWS WIRQSPGKGLEWIA EINDSG ADI-21021 Heavy chain variable region

NTNHNPSLKS RVTISIDTSKNQFSLNVSSVTAADTAVYYC AKNGGGHHYVGTLRFRS (“HC”) amino acid sequence

RAFDI WGQGTMVTVSS

Ab 270 540 EIVMTQSPSTLSASVGDRVTITC RASQSIGNRLA WYQQKPGKAPKLLIS LASGLET GV ADI-21021 Light chain variable region

PSRFSGSGSGTEFTLTITSLQPDDFATYYC QQYSSYGT FGQGTKLEIK (“LC”) amino acid sequence

Ab 271 541 EVQLVETGPGLVKPSETLSLTCSVSG GSISSYYWS WLRQPPGKGLEWIG YIYNSGRT ADI-21022 Heavy chain variable region

NYNPSLRS RVTISVDTSQNQFSLRLGSVTAADTAVYYC ARGGAGDDLLRGSYRYLNF (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 271 542 QSVLTQPPSVSVAPGQTARITC GGNNIGSKSVH WYQQKPGQAPVLVVY DDTERPS ADI-21022 Light chain variable region

GIPERISGSNSGNTATLTISRVEAGDEADYYC QVWDSSSDHPDLL FGGGTKLTVL (“LC”) amino acid sequence

Ab 272 543 EVQLVESGGGLVKPGGSLRLSCAASG FRFSSYGMH WVRQAPGRGLEWVS SITAGS ADI-21023 Heavy chain variable region

SYMDYADSVKG RFSISRDNAKTSLYLQMNSLRAEDTAIYYC ARENYDTGRGLNWF (“HC”) amino acid sequence

DP WGQGTLVTVSS

Ab 272 544 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYRQLPGTAPEVLIY GNNN ADI-21023 Light chain variable region

RPS GVPDRFSGSKTGTSASLAITGLLAEDGADYYC QSYDRSQLWV FGGGTQLTVP (“LC”) amino acid sequence

Ab 273 545 EVQLVESGGGLVRPGGSLRLSCEASGLKLSGYSMNWVRQAPGKGLEWVSSISASSS ADI-21025 Heavy chain variable region

YIHYADSLKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCVASWLTPGWFDPWGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 273 546 QPVLTQPPSVSGAPGQTVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNTNR ADI-21025 Light chain variable region

PS GVPDRFSGSKSGTSASLAVTGLQAEDEGDYYC QSYDSSLSGSA FGGGTKLTVL (“LC”) amino acid sequence

Ab 274 547 QVQLVQSGPGLVKPSQTLSLTCTVSG VSISSGGFYW SWIRQHPGKGLEWIG HIYYS ADI-21026 Heavy chain variable region

RSTYYNPSLKS RVTMSLNMSKNQFSLRLSSVTAADTAVYYC ARERREWLHGELDY (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 274 548 DIQMTQSPDSLAVSLGEGATINC KSSQSVLDSSKNKNYLA WYQQRPGQPPKLLIS W ADI-21026 Light chain variable region

ASTRES GVPDRFSGSGSGTDFTLTISSLQAEDVAVYSC QQYFSPPAT FGQGTKLEIK (“LC”) amino acid sequence

Ab 275 549 QVQLQESGPGLVKPSGTLSLTCVVSG GSIRSHNYWT WVRQPPGKGLEWIG EIYHS ADI-21027 Heavy chain variable region

GNTNYNPSLKS RVTLSIDKSKNVFSLRLNSVTAADTAVYYC VGGGPFAPYYFEN WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 275 550 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYAVH WYHQLPGTAPKLLIY DNNNR ADI-21027 Light chain variable region

PS GVPDRFSGSKSGSSASLAITGLQAEDEADYYC QSYDRSLSGYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 276 551 EVQLVESGGALVKPGGSLRLSCVASG FTFSDYYMH WVRQAPGKGLEWVS YISSTSS ADI-21028 Heavy chain variable region

FTNYADSVKG RFIISRDNAKNSLYLQLNSLRAEDTAVYYC ARDESSGWQTRRHFGM (“HC”) amino acid sequence

DV WGQGTLVTVSS

Ab 276 552 EIVMTQSPSTLSASVGDRVTITC RASQSLNTWLA WYQHKPGKAPKLLIS TASSLQS G ADI-21028 Light chain variable region

VPSRFSASGSGTEFTLTISSLQPDDFATYYC QQFRGT FGPGTKVEIK (“LC”) amino acid sequence

Ab 277 553 QVQLVQSGAEVRKPGESLKISCKASG YSFTNYWIG WVRQMPGKGLEWMG IVYPA ADI-21029 Heavy chain variable region

DSHPVYSPSFQG QVTFSTDKSINTAYLQWSSLKASDTAMYFC ARRDGGTDYLSDAF (“HC”) amino acid sequence

DI WGQGTMVTVSS

Ab 277 554 DIVMTQSPSSLSASVGDRVTITC RTSQSIRRYLN WYQQKPGKAPKLLIY AASSLQS GV ADI-21029 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPNT FGQGTKVEIK (“LC”) amino acid sequence

Ab 278 555 EVQLVESGGGLVKPGGSLRLSCAASG FKFSTYYMS WIRQAPGKGLEWVS NISGGSS ADI-21030 Heavy chain variable region

YSNHADSVKG RFTISRDNAKNSLYLEMNSLRAEDTAVYYC AREDLMGVSGLAYFEY (“HC”) amino acid sequence

WGQGILVTVSS

Ab 278 556 QPVLTQPPSVSGAPGQRVTISC TGRSSNIGAGYDVN WYKQLPGAVPKVLIY GNTNR ADI-21030 Light chain variable region

PS GVPDRFSGSKSGNSASLAITGLQAEDEADYYC QSYDRNLGYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 279 557 EVQLVESGPGLVKPSQTLSLTCTVSG GSISNSNYFWS WIRQPAGKGLEWIG RVHSS ADI-21031 Heavy chain variable region

GTTSYNPSLKS RITISVDASESQFSLNLTSVTAADTAIYYC ARDSSDWGLGWYFDL W (“HC”) amino acid sequence

GRGTLVTVSS

Ab 279 558 ETTLTQSPATLSLSPGERATLSC RASQSVTFYLA WYQHKPGQAPRLLIF DASKRAT GI ADI-21031 Light chain variable region

PARFSGSGSGTDFTLTISSLEPEDFALYYC QQRSDWPQT FGQGTKVDIK (“LC”) amino acid sequence

Ab 280 559 EVQLVESGGGLVKPGGSLRLSCAVSG FKFSSYTMN WVRQAPGKGLEWVS SVSASS ADI-21032 Heavy chain variable region

SYIFYADSVQG RFIISRDNAQNSLYLQMNSLRADDTAVYYC TRDQYGPGHYYNPA (“HC”) amino acid sequence

WFDP WGQGTLVTVSS

Ab 280 560 QPVLTQPPSASGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKVLIY GNTNR ADI-21032 Light chain variable region

PS GIPDRFSGSKSGTSASLAIIGLQAEDEADYYC QSYDRNGSKV FGTGTKLTVL (“LC”) amino acid sequence

Ab 281 561 QVQLVQSGAEVRKPGDSLKISCKFSE NIFTTYYWTG WVRQMPGRGLEWMG IIFPG ADI-21033 Heavy chain variable region

DSDTRYSPSFQG HVTISVDKSIATAFLQWSSLKASDSAMYYC ARAKYEGSFDM WG (“HC”) amino acid sequence

QGTMVTVSS

Ab 281 562 DIQVTQSPSSLSASVGDRVSITC QASQDIRNRLN WYQQKPGKAPKLLIY DASILET GV ADI-21033 Light chain variable region

PSRFSGSGSGTDFTFSISSLQPEDFATYYC QQYDSFSLFT FGPGTKVEIK (“LC”) amino acid sequence

Ab 282 563 QVQLQQSGAEVKKPGESLTISCKGSG YSFGNYWIS WVRQMPGKGLEWMG RIDPS ADI-21034 Heavy chain variable region

DSYVNYSPSFQG NVTMSVDKSSSTAYLQWSSLKASDTAMYYC ARLAGYSTL WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 282 564 EIVLTQSPGTLSLSPGERATLSC RASQSFGSIYLA WYQQKPGQAPRLLIY GTSSRAT GI ADI-21034 Light chain variable region

PDRFSGSGSGTDFTLTIRRLEPEDFAVYYC LYYGSSPGAT FGPGTKVDIK (“LC”) amino acid sequence

Ab 283 565 EVQLVESGHEVKKPGASVKVSCKASG YTFPSYGIS WVRQAPGQGLEWMG WIVPY ADI-21035 Heavy chain variable region

NGNTKYAQRFQG RITMTTDSPTSTASMELRGLRSDDTAVYYC ARVFGDGYSYGYE (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 283 566 DIVLTQSPSTLSASVGDRVTITC RASQSISIWLA WYQQKPGKAPKLLIY KTSELVS GVP ADI-21035 Light chain variable region

SRFSGSGSGTEFTLTISGLQPDDFATYYC QQGNSYSHT FGQGTKVEIK (“LC”) amino acid sequence

Ab 284 567 QVQLVQSGAEVKEPGKSLKISCKGSG NHFGNYWIA WVRQMPGKGLEWMG IIYPG ADI-21036 Heavy chain variable region

DSDTRYSPSFQD QVTISVDKSINTVYLQWSSLKAADTATYYC AGSKLGNSWYTIYDS (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 284 568 NFMLTQPASVSGSPGQSITISC AGPSALIGVYNLVS WYQQVPGKAPKLIIY EGSKRPS ADI-21036 Light chain variable region

GVSHRFSGSKSGYTASLTISGLQTEDEADYYC CSYAGSGTSVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 285 569 QVQLVQSGGGVVQPGRSLRLSCAASG FPFSSYAMH WVRQAPGKGLEWVA VIWY ADI-21037 Heavy chain variable region

PGGEKYSADSVTG RFTISRDNSKNTLYLQMSSLRVEDTAVYYC ARRSVGAFDY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 285 570 DIQMTQSPLSLPVTPGEPASISC RSSQSLLNSNGYNYLD WYLQKPGQSPQVLIY LGS ADI-21037 Light chain variable region

HRAS GVPDRFSGSGSGTDFTLRISRVEAEDVGVYYC MQAVQTPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 286 571 QVQLVQSGAEVKKPGESLKISCQGFG FSFTSYWIG WVRQTPGKGLEWMG TIYPGD ADI-21038 Heavy chain variable region

SETRKSPSIQG QVTFSADRSISTAYLQWSGLTASDTAVYYC ARLKGGWGTTMAGIR (“HC”) amino acid sequence

DYFYYGLDV WGQGTTVTVSS

Ab 286 572 EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLIY GASSRAT G ADI-21038 Light chain variable region

IPDRFTGSGSGTDFTLTISRLEPEDFAVYYC QQYATSLGGFT FGPGTKVDIK (“LC”) amino acid sequence

Ab 287 573 EVQLVQSGAEVKKPGASVKVSCKASG YTFISYYIH WVRQAPGQGLEWMG VINPSG ADI-21039 Heavy chain variable region

GITDYAPKFQG RVSMTRDTSTRTVYLELSSLRSDDTAVYYC ARDLCITTSCPRYYDYA (“HC”) amino acid sequence

WRSYRSEGYFDS WGQGTLVTVSS

Ab 287 574 EIVMTQSPLSLPVTPGEPASISC RSSQSLLHSNGYNYLD WYLQKPGQSPQLLIY LGSN ADI-21039 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQAQQAPFT FGGGTKVEIK (“LC”) amino acid sequence

Ab 288 575 EVQLLESGPGLVKPSGTPSLTCAVSG VSITNSNNWWT WVRQPPGKGLEWIG EIYSS ADI-21040 Heavy chain variable region

GSTNYSPSLKS RVTISLDKSKNQFSLKLSSVTAADTAVYYC ARVLGYYGSGGGHLHS (“HC”) amino acid sequence

WGPGTLVTVSS

Ab 288 576 SYELTQPPSASGTPGQRVTISC SGSSSNIGAGYDVH WYQQLPGTAPKLLIS VNSNRP ADI-21040 Light chain variable region

S GVPDRFSGSKSGTSASLAITGLQAEDEANYYC QSYDNSLSGYVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 289 577 EVQLVESGGVVVQPGGSLRLSCAASG FTFDDYTMH WVRQAPGKGLEWVS LISWV ADI-21041 Heavy chain variable region

GDTTYYADSVKG RFTISRDNSKNSLYLQMNSLRTEDTALYYC AKGGYYDGSGYYYFD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 289 578 DIRLTQSPSSLSASVGDRVTITC RASQSISNYLN WYQQKPGKAPKLLMY AASSLQS G ADI-21041 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYSC QQSYSTPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 290 579 EVQLVESGPRLVKPSQTLSLTCNVSG VPVNTGGYYWS WIRRHPIKGLEWIG YIYYSG ADI-21042 Heavy chain variable region

STHYNPSLRG RATMSVDTSKNQFSLRLSSVTAADTAVYYC AKDTITVLRGVAKKGVF (“HC”) amino acid sequence

DP WGQGILVTVSS

Ab 290 580 DIQMTQSPSTLSASVGDRVIITC RASQSISSWLA WYQYKPGKAPNLLIY KATTLDS G ADI-21042 Light chain variable region

VPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQYDSYPT FGQGTKVEIK (“LC”) amino acid sequence

Ab 291 581 QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYGIT WVRQAPGQGLEWMG WISTY ADI-21043 Heavy chain variable region

NGKTNYAQKFKG RVTMTTDTSTSTAYVELTSLRSDDTAVYYC AREFPTRIVDSFYM (“HC”) amino acid sequence

DV WGKGTTVTVSS

Ab 291 582 SYELTQPPSVSVAPGQTARITC GGSNIGSETVH WYQQKPGQAPVLVVY GDSDRPS ADI-21043 Light chain variable region

GIPERFSGSNSGNTATLTISRVEAGDEADYYC QVWDSRSDDFHV FGSGTKLTVL (“LC”) amino acid sequence

Ab 292 583 QVQLVQSGAELKKPGESLKISCKTSG YTFANYWIG WVRQMPGKGLEWMG IIYPGD ADI-21044 Heavy chain variable region

SDTRYSPSFQG QVTFSADKSINSAYLQWHSLKASDSAIYYC ARRFSPDYSDGAAPPT (“HC”) amino acid sequence

LSDAFDV WGQGTTVTVSS

Ab 292 584 DIVMTQSPSSLSASVGDRVTITC RASQNINIYLN WYQQKPGKAPKLLIY AASTLQS G ADI-21044 Light chain variable region

VPSRFSGSGSATDFTLTISSLQPEDFATYYC QQSYRTPND FGRGTKVDIK (“LC”) amino acid sequence

Ab 293 585 EVQLVESGGGLVKPGGSLRLSCLASG FKFRSYSMN WVRQAPGTGLVWVA SISASSS ADI-21045 Heavy chain variable region

FIFYADSLKG RFTISRDNDKNSLYLQMNSLTVEDTAVYYC VRDMSGISSGGKTFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 293 586 QSVLTQPPSVSGAPGQRVTISC TGSSSNLGAGYDVQ WYQQLPGTAPKLLIY GNNN ADI-21045 Light chain variable region

RPS GVPDRFSGSKSGTSASLAITGLRAEDEADYYC QSYDTSPV FGGGTKLTVL (“LC”) amino acid sequence

Ab 294 587 EVQLVESGAEAKKPGESLRISCTVSG YSFSKYWVG WVRQTPGKGLEWMG IIDPTDS ADI-21046 Heavy chain variable region

DTRYSPSFQG QVTISVDNSINTAYLQWSSLKASDTAIYYC ARRGQAKCVGNCPRDF (“HC”) amino acid sequence

MDV WGKGTTVTVSS

Ab 294 588 SYVLTQPPSVSGAPGQRVTISC AGSSSNIGAGYEVH WYQQLPGTAPKLLIY ANRNR ADI-21046 Light chain variable region

PS GVPDRFSGSRSGTSASLAISGLQAEDEADYYC QSYDNNLSGSWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 295 589 QVQLQQWGAGLLKPSETLSLTCAVYG GSFSGKYWS WIRQPPGKGLEWIG EFNHD ADI-21047 Heavy chain variable region

GTTYYNPSLKS RVTISADTPKNQFSLTLHSVTAADTAVYYC ARLTILSD WGQGTLVTV (“HC”) amino acid sequence

SS

Ab 295 590 DIRMTQSPSSLSASVGDRVTITC QASQDISNYLH WYQQKPGKAPKLLIY DASNLET G ADI-21047 Light chain variable region

VPSRFSGSGSGTDFTFTIHSLQPEDLATYYC QQYYDLPRT FGQGTKLEIK (“LC”) amino acid sequence

Ab 296 591 EVQLVESGAEVKKPGASVKVSCKASG YTFSSHAIS WVRQAPGHGLEWMG WISVF ADI-21048 Heavy chain variable region

NGNTNYAQKFQG RVTMTTDTSTSTAYMELRSLRSDDAAVYYC AREVIGVGEFYFD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 296 592 QSVLTQPPSVSVAPGQTARITC GGNNIGSKSVH WYQQKAGQAPVLVVY DDSDRPS ADI-21048 Light chain variable region

GIPERFLGSNSGNTATLTISRVEAGDEADYYC QVWDSSGDFHV FGTGTKVTVL (“LC”) amino acid sequence

Ab 297 593 EVQLVESGGGLVKPGGSLRLSCSASG FAFSSYSMN WVRQAPGKGLEWVS SISASSS ADI-21049 Heavy chain variable region

YIFYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAFYYC ARALSPGYGDYRDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 297 594 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGAAPKLLIY GNNN ADI-21049 Light chain variable region

RPS GVPDRFSGSKSGTSASLAITGLQAEDEADFYC QSYDHNLSVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 298 595 QVQLVQSGAEVKKPGASVKVSCTASG YTFANNGIS WVRQAPGQGLEWMG WISA ADI-21050 Heavy chain variable region

YNGNTKYAQTVQG RVILTIDTSTSTAYMELRSLTSDDTAVYYC AREMGVDAAATF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 298 596 EIVMTQSPLFLSVTLGQPASISC RSSQSLVYSDTNTYL TWFQQRPGQSPRRLIY KVSN ADI-21050 Light chain variable region

RDS GVPDRFSGSGSGTYFTLKISRVEAEDIGVYYC MQAIHWPRT FGQGTKLEIK (“LC”) amino acid sequence

Ab 299 597 QVQLVESGPGLVRPSQTLSLTCNVSG DFISRGTYYWS WIRQSAGKGLEWIG RIYTS ADI-21051 Heavy chain variable region

GITDYSPSLKS RVTISVDTSKNQFFLKLASVTAADTAVYYC ARGRGYYDSP WGQGTL (“HC”) amino acid sequence

VTVSS

Ab 299 598 ETTLTQSPATLSLSPGERATLSC RASESVSTFLG WYQQKPGQAPRLLIY DASNRAS G ADI-21051 Light chain variable region

VPARFSGSGSGTDFTLTISSLEPEDFAVYYC QLRNKWLT FGPGTKVDIK (“LC”) amino acid sequence

Ab 300 599 QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYGIS WVRQAPGQGLEWMG WISAY ADI-21052 Heavy chain variable region

NGNTNYAQNLQG RVTMTTDTSTSTAYMELRSLRSDDTAMYYC ARDAFSRVGYWY (“HC”) amino acid sequence

FDL WGRGTLVTVSS

Ab 300 600 SYELTQPPSVSVAPGQAARITC GGNNIGSKTVH WYQQKPSQAPVLVVY DDSDRPS ADI-21052 Light chain variable region

GIPERFSGSNSGNTATLTISRVEAGDEADYYC QVWDSSGDHPV FGGGTKLTVL (“LC”) amino acid sequence

Ab 301 601 QVQLQESGPGLVKPSQTLSLTCTVSG VSISNSSGGYYWS WIRQHPGKGLEWIG YIYY ADI-21053 Heavy chain variable region

SGSTYYNPSSGSTYYNPSLKS RVTVSVDTSKNQFSLKLTSVTAADTAVYYC ARDIRGP (“HC”) amino acid sequence

HKHSLYNWFHP WGQGTLVTVSS

Ab 301 602 DIQMTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIY AASSLQT G ADI-21053 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTLRT FGQGTKVDIK (“LC”) amino acid sequence

Ab 302 603 QVQLVESGGGVVQPGRSLRLSCAASG FSFSNYGMH WVRQAPGKGLEWVV GISFD ADI-21054 Heavy chain variable region

GSYIFHGGSVTG RFNISRDNSKNTLYLQVNSVRAEDTAVYYC ARDPQYYDDWSGYS (“HC”) amino acid sequence

GLLHYYLYMDV WGKGTTVTVSS

Ab 302 604 DIQLTQSPSTLSASVGDRVTITC RASQSIGTSLA WYQQIPGKAPKLLIY RASSLES GVP ADI-21054 Light chain variable region

SRFSGGGSGTQFTLTISSLQPDDFATYYC QQYNNYSPT FGQGTKLEIK (“LC”) amino acid sequence

Ab 303 605 EVQLVESGGGVVQPGRSLRLSCVGSG FTFSRYGMQ WVRQAPGKGLEWAA VIWN ADI-21055 Heavy chain variable region

DGSNEHYADSVKG RFTISRDNSKNTMYLQMNSLRAEDTALYYC AREGEYSSSWSH (“HC”) amino acid sequence

WSYLDL WGRGTLVTVSS

Ab 303 606 QPGLTQPPSASGTPGQRVTISC SGSTSNIGGNTVN WYQQLPGTAPTVLIY QNRQRP ADI-21055 Light chain variable region

S GVPDRFSGSKSGTSASLAISGLQSDDEADYYC AAWDDSLNGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 304 607 EVQLLESGGGLVKPGGSLKLSCAASG FTLRSYYMH WVRQAPGRGLEWVS SISASSS ADI-21056 Heavy chain variable region

YINYVDAVKG RFTVSRDNAKNSLFLQMNSLRAEDTAVYYC AREGGAMTNFGVVIDI (“HC”) amino acid sequence

WGQGTMVTVSS

Ab 304 608 SYVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY TNTNRP ADI-21056 Light chain variable region

S GVPDRFSGSKSGTSASLAITGLQSDDEADYYC QSYDSSLSGPVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 305 609 QVQLVQSGAEVKKPGESLKISCKASG YSLSNNWIA WVRQMPGKGLEWMG IVYLG ADI-21057 Heavy chain variable region

DSDARYSPSFQG QVTFSADKSISTAYLQWSSLQASDTAMYFC ARHHGDLVVTSDSR (“HC”) amino acid sequence

YFYGLDV WGQGTTVTVSS

Ab 305 610 DIVMTQSPATLSVSPGERATLSC RASQSISSNLA WYQQKPGQAPRLLIY GASTRAT G ADI-21057 Light chain variable region

IPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPPSDT FGQGTRLEIK (“LC”) amino acid sequence

Ab 306 611 QVQLQESGPGLVKPSETLSLTCTVSG GSISGTTYYWA WIRQPPGKGLEWIG TIFYSG ADI-21058 Heavy chain variable region

STYYNPSLQS RVTTSVDASKNQMSLRLSSVTAADTAMYYC ARHTSIYDNLTGFYSHL (“HC”) amino acid sequence

TGVLDM WGQGTMVTVSS

Ab 306 612 DIQLTQSPATLSVSPGERATLSC RASQSVSTNLA WYQQKRGQAPRLLIY GASTRAI GI ADI-21058 Light chain variable region

PARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPPAYT FGQGTKVDIK (“LC”) amino acid sequence

Ab 307 613 QVQLVQSGAEVKRPGDSLKISCKGSG YSFTTSWIG WVRQVPGKGLEWMG IIYPGD ADI-21059 Heavy chain variable region

SNTVYGPSLQG QVTISADKSTNTAYLQWSSLKASDTAMYYC ARRDGGTDYLSDAF (“HC”) amino acid sequence

DI WGQGTFVTVSS

Ab 307 614 DIQMTQSPSSLSASVGDRVTITC RTSQNIVIYLN WYQQKPGKAPKLLIF AASSLPS GV ADI-21059 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDVATYYC QQSYNTPGT FGQGTKVDIK (“LC”) amino acid sequence

Ab 308 615 EVQLVESGGGLVKPGGSLRLSCEASG FRLSDYYMT WIRQAPGKGLECIS YISGGSTF ADI-21060 Heavy chain variable region

KSYSDSVKG RFTISRDNTNLYLQMNSLRVEDTAVYYC ARAPYLIYYMDV WGKGTTV (“HC”) amino acid sequence

TVSS

Ab 308 616 QPVLTQPPSVSGAPGQRVSISC TGSNSNIGAGYDVH WYQQLPGTPPKLLIY DNNN ADI-21060 Light chain variable region

RPS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDNRLSGSQVL FGGGTKVTV (“LC”) amino acid sequence

L

Ab 309 617 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSNYPIS WVRQAPGHGLEWMG RVVPT ADI-21061 Heavy chain variable region

VGLANYAQNLQG RVTITADTSTNTVYMELRSLRSEDTGLYYC ARRAVVDTYAFDI W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 309 618 QSALIQPASVSGFPGQSITISC TGASSDVGGYNFVS WYQQHPGKAPKLIIY EVTKRPS ADI-21061 Light chain variable region

GVSNRFSGSESGNTASLTISGLQAEDEADYYC SSFRYTSSIVYV FGSGTKVTVL (“LC”) amino acid sequence

Ab 310 619 EVQLLESGGGLVKPGGSLRLSCAASG FTFSDYDM IWVRQAPGKGLEWVS SISRGSD ADI-21062 Heavy chain variable region

YIYYADSLKG RFTISRDNARNSVTLQMNSLRAGDTALYFC ARAELLDSGGYYLYYFD (“HC”) amino acid sequence

H WGQGTLVTVSS

Ab 310 620 DIRMTQSPSSLSASVGDRVTITC RASQIIASYVN WYQKKPGKAPKVLIY AASRLQN G ADI-21062 Light chain variable region

VPSRFSGSGSGTEFTLTISSLQPEDFATYYC QQSYSTSFT FGQGTKVDIK (“LC”) amino acid sequence

Ab 311 621 EVQLVESGGGLVQPGGSLRLSCSASG FTFRTYVMQ WVRQAPGKGLEYVS AISSDG ADI-21063 Heavy chain variable region

GSTDYADSVKG RFTVSRDNSKNTLYLQMSSLRAEDTAVYYC VKRGEGGNDYLYYY (“HC”) amino acid sequence

MDV WGKGTTVTVSS

Ab 311 622 DIQVTQSPSSLSASVGDRVTITCR ASQSITNYLN WYQQKPGKAPKVLIY AASSLQS G ADI-21063 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYLRPPT FGGGTKVEIK (“LC”) amino acid sequence

Ab 312 623 EVQLVESGGEVKKPGASVKVSCKASG YIFSNHGVS WVRQAPGQGLEWMG WISAY ADI-21064 Heavy chain variable region

NGNAIYAQNLQG RVILTIDTSTSTAYMELTSLTSDDTAIYYC ARESGATAAAVMDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 312 624 DIVLTQTPLSLPVILGQPASISC RSSQSLVYSDGNTYLT WFQQRPGQSPRRLIY KVSN ADI-21064 Light chain variable region

RDS GVPDRFSGSGSDTDFTLKISRVEAEDVGVYYC MQGIDWPRT FGQGTKVDIK (“LC”) amino acid sequence

Ab 313 625 EVQLLESGGGLVQPGGSLRLSCAASG FTFSSYAMN WVRQAPGKGLEWVS GISGSG ADI-21065 Heavy chain variable region

ESTYYADSVKG RFTISRDSSKNTVYLQMNSLRADDTAVYYC AKDQGYGVVVPAATR (“HC”) amino acid sequence

ALPPRRYGMDV WGQGTTVTVSS

Ab 313 626 EIVLTQSPGTLSLSPGERATLSC RASQSVSSTYLA WYQQKPGQAPRLLIY GASSRAT G ADI-21065 Light chain variable region

IPDRFSGSGSGTDFTLTITRLEPEDFAVYYC QQYGSSPPLT FGGGTKVDIK (“LC”) amino acid sequence

Ab 314 627 QVQLQESGPGLVKPSGTLSLICVVSG GSIKSHNYWT WVRQPPGKGLEWVG EIYQS ADI-21068 Heavy chain variable region

GRTNYNPSLNS RVTLSMDKSKNQLSLRLTSVTAADTAVYFC VGGGPFAPYYFQT W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 314 628 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY NNNNR ADI-21068 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDTSLSGYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 315 629 EVQLVESGAEVRKPGASVKVSCKASG YTFSSNAIS WVRQAPGQGLEWMG YISVFN ADI-21069 Heavy chain variable region

GNTKYAQNLQG RVTMTTDTATSTVYMELRSLRYDDTAIYYC ARESLGMGGFYFDH (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 315 630 SYELTQPPSVSVAPGQTARITC GANNIGSDSVH WYQQKPGQAPVLVVF DDRDRPS ADI-21069 Light chain variable region

GIPERFSGSNSGNTATLTISRVEAGDEADYYC QVWMTSDRSV FGGGTKLTVL (“LC”) amino acid sequence

Ab 316 631 EVQLVESGGGLVQPGGSLRLSCAASG FTFSRYAMG WVRQAPGKGLEWVS TISDSG ADI-21070 Heavy chain variable region

GSTFYADSVEG RFTIARDSSKNTLSLHMNSLRAEDTAIYYC AREAYSSSWYSGGWFD (“HC”) amino acid sequence

R WGQGTLVTVSS

Ab 316 632 ETTLTQSPATLSVSPGERATLSC RASQSVSSNLA WYQQKPGQAPRLLIY GASTRAT G ADI-21070 Light chain variable region

IPARFSGSGSGAEFTLTINSLQSEDFAIYYC QQYNNWPQYT FGQGTKVDIK (“LC”) amino acid sequence

Ab 317 633 EVQLVESGGGVVQPGKSLRLSCAVSG FTFSDHDMH WVRQAPGKGLEWVA AIWS ADI-21071 Heavy chain variable region

DRTTKYYGDFVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARGQIYKSGGYYLV (“HC”) amino acid sequence

HLDH WGQGTLVTVSS

Ab 317 634 DIQVTQSPSSLSASVGDRVTITC RASQSIASYLN WYQQKPGKAPNLLIY AASNLQS E ADI-21071 Light chain variable region

VPSRFSGSGSGTDFTLTISGLQPEDFATYYC QQSYNIRLLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 318 635 QVQLVQSGGGLVKPGGSLRLSCEASG FNFRSYHMS WVRQAPGKGLEWVS SITAG ADI-21072 Heavy chain variable region

SSYINYADSVKG RFTISRDNAKNSVLQMNSLSAEDTAVYYC AREGLNMGVGGTW (“HC”) amino acid sequence

FDP WGQGTLVTVSS

Ab 318 636 QAVVTQEPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNNN ADI-21072 Light chain variable region

RPS GVPDRFSGSKSATSASLAITGLQADDEADYYC QSYDRSLSGSWV FGIGTKVTVL (“LC”) amino acid sequence

Ab 319 637 EVQLVESGGGLVRPGRSLRLSCAASG FTFSMFSMN WVRQAPGKGLEWLA YIGGS ADI-21073 Heavy chain variable region

GSTIDYANSVSG RFTISRDNAKNSLYLQMNSLRDEDTAVYYC ARIGLQTYNSHSSSSS (“HC”) amino acid sequence

PARAFDV WGQGTTVTVSS

Ab 319 638 DIVLTQSPSSLSASVGDRVTITC RASQSIGRFLN WYQQKPGKAPKLLIY AASSLES GV ADI-21073 Light chain variable region

PSRFSGSGSGTQFSLTISSLQPEDFTTYYC QQSYSTPTT FGGGTKVDIK (“LC”) amino acid sequence

Ab 320 639 EVQLVESGGGLVKPGGSLRLSCAASG FSFSNYYMS WVRQAPGKGLEWIS YISGGST ADI-21075 Heavy chain variable region

YANLADSVKG RFTISRDNTKNSMYLQMTSLRPDDTAVYYC ARIHGTHGPFYFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 320 640 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIH ANSNR ADI-21075 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDNSLNAYYVF GTGTKLTVL (“LC”) amino acid sequence

Ab 321 641 EVQLVESGGGLVRPGGSLRLSCAASG FTFSSYAMD WVRQAPGKGLEWVS SISASSS ADI-21076 Heavy chain variable region

FISYTDSVKG RFTISRDNAKNSLFLQMDNVTAEDTAVYYC ARDYYESGRYFYGNPFD (“HC”) amino acid sequence

I WGQGTMVTVSS

Ab 321 642 QPVLTQPPSVSGAPGQRVTISC TGSGSNIGAGFDVH WYQQLPGTAPKLLIY ANSDR ADI-21076 Light chain variable region

PS GVPDRFSASKSGTSASLAITGLQAEDEAHYYC QSYDNSLGGLCV FGIGTKLTVL (“LC”) amino acid sequence

Ab 322 643 QVQLVESGGGLVKPGGSLRLSCVVSG FTFRDYYMS WIRQAPGKGLEWIS YISPSSTY ADI-21077 Heavy chain variable region

TNYADSVRG RFTISRDNAENSLYLQMNSLRAEDTAVYYC ARVNIAATGAGGVFLDY (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 322 644 QPVLTQPPSVSGAPGQRVTISC AGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNINR ADI-21077 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSYV FGIGTKVTVL (“LC”) amino acid sequence

Ab 323 645 EVQLVESGGGLVKPGGSLRLSCAASG FRLSDYYMS WIRQAPGKGLEWIS DISGGST ADI-21078 Heavy chain variable region

YTNYADSVKG RLTISRDNAQNSLYLQMNSLRAEDTAVYYC ARWGSGGPDAFHF W (“HC”) amino acid sequence

GQGTTVTVSS

Ab 323 646 QSVLTQPPSVSGVPGQRVTISC TGSRSNIGAGYDVH WYRQLPGTAPKLLIY GNSNR ADI-21078 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQADDEADYYC QSYDSSLSGSVI FGGGTKVTVL (“LC”) amino acid sequence

Ab 324 647 EVQLLESGGGLVKPGGSLRLSCAASG FTFSDYYMS WIRQAPGKGLEWVS NISGGST ADI-21079 Heavy chain variable region

YTNYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREAYGSGNYYNPNW (“HC”) amino acid sequence

LDP WGQGTLVTVSS

Ab 324 648 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNRNR ADI-21079 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV FGGGTKLTVL (“LC”) amino acid sequence

Ab 325 649 EVQLLESGGGLVKPGGSLRLSCEVSG FRLSDYYMS WIRQAPGKGLEWVS HISGGST ADI-21080 Heavy chain variable region

YTNYADSVKG RFTISRDNGKKSMYLQMNSLRAEDTALYYC AKWGSGGPEAFDI W (“HC”) amino acid sequence

GRGTMVTVSS

Ab 325 650 QSALIQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQIPGTAPKWY GNNNR ADI-21080 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDNSLSGSVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 326 651 EVQLLESGGGLVKPGGSLRLSCAASR FAFSNYYMT WIRQAPGKGLEWIS NISGGSTF ADI-21081 Heavy chain variable region

TNYADSVKG RFTISRDNAKNSVHLQMNSLRAEDTAVYYC VREASVAAGTPEGFDI (“HC”) amino acid sequence

WGQGTMVTVSS

Ab 326 652 QSVLTQPPSVSGAPGQRVIISC TGSSSNIGAGYDVN WYQQLPGTAPKLLMY GNRN ADI-21081 Light chain variable region

RAS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC HSYDSSLGGSV FGGGTKLTVL (“LC”) amino acid sequence

Ab 327 653 EVQLVESGGGLVKPGGSLKLSCVASG LKFSSYSMN WVRQAPGKGLEWVS SVSAGS ADI-21082 Heavy chain variable region

SYTNYADSVKG RFTISRDNAKNSLYLQMNSLRVDDTAVYYC ATERCSGGSCYLHGF (“HC”) amino acid sequence

DP WGQGTTVTVSS

Ab 327 654 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIF DNIIRP ADI-21082 Light chain variable region

S GVPDRFSGSKSGTSASLAITGLQADDEADYYC QSYDKSGDYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 328 655 QVQLQESGPGLVKPSGTLSLICAVSG DSITTSNWWS WVRQPPGKGLEWIG EIYHS ADI-21083 Heavy chain variable region

GVTRYNPSLKS RLSISLDKSRNQFSLKLSSVTAADTAVYYC ARDEALFGHWFDP WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 328 656 QSVLTQPRSVSGSPGQSVTISC TGSSSDIGSYNYVS WYQQHPGKAPKLMLY DVSKR ADI-21083 Light chain variable region

PS GVPDRFSGSKSVKTASLTISGLQAEDEADYYC CTYAGNSVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 329 657 EVQLVESGAEVKKPGASVTVSCKASG YTFTSNTIS WLRQAPGQGLEWLG WVSASN ADI-21084 Heavy chain variable region

GNTKYAQKFQG RVTMTTDTSATTAYMEVRTLRHDDTAIYYC ARDILDMGGFHFD (“HC”) amino acid sequence

N WGQGTLVTVSS

Ab 329 658 SYVLTQPPSVSVAPGQTARITC GGNNIGNKHVH WYKQKPGQAPVLVVY DDSDRPS ADI-21084 Light chain variable region

GIPERFSGSNSGNTATLTVSRVEAGDEADFYC QVWDNTNDHPV FGGGTKVTVL (“LC”) amino acid sequence

Ab 330 659 EVQLVETGGGLVKPGGSLRLSCEASG FNFRSYSMN WVRQAPGKGLEWVS SISASSS ADI-21085 Heavy chain variable region

YINYADSVKG RFTISRDNSKNSLYLQMNSLRAEDTGVYYC ARVLVHYYYGMDV WG (“HC”) amino acid sequence

QGTTVTVSS

Ab 330 660 QSVLTQPPSVSAAPGQRVTISC TGTSSNIGAGYDVH WYQQLPGRAPKLLIL GNNNR ADI-21085 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QTYDKTLMEI FGGGTKLTVL (“LC”) amino acid sequence

Ab 331 661 EVQLVETGGGLVKPGGSLRLSCAASP FAFSNYYMS WIRQAPGKGLEWIS NISGGST ADI-21086 Heavy chain variable region

FTNYADSVKG RFTISRDNARNSLYLLMNNLRTEDTAVYYC AREASVAAGTPEGFDV (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 331 662 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVN WYQQFPGTAPKLLIY GNRNR ADI-21086 Light chain variable region

PS GVPARFSGSKSGASASLAITGLQAEDEADYYC HSYDSGLSGSV FGGGTKLTVL (“LC”) amino acid sequence

Ab 332 663 EVQLVESGGGLVQPGGSLRLSCAASG FTFSGYEMN WVRQAPGKGLEWLS YISSSG ADI-21087 Heavy chain variable region

GIIYYADSVKG RFTISRDNARNSLFLQMNSLRAEDTAVYSC ARARLLDGFDI WGQGT (“HC”) amino acid sequence

MVTVSS

Ab 332 664 DIQVTQSPSTLSASVGDRVTITC RASQSIGSWLA WYQQKPGKAPKLLIY KASSLES G ADI-21087 Light chain variable region

VPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQYNSYSYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 333 665 EVQLLESGGGLVKPGGSLRLSCVASG FRFTSYSMN WVRQAPGKGLEWVS SISASSS ADI-21089 Heavy chain variable region

YVDYADSLKG RFTISRDNAQNSLFLQMNSLRAEDTAVYYC ARDYYDSGNYHSPFP (“HC”) amino acid sequence

MDV WGQGTTVTVSS

Ab 333 666 QSVLTQPPSVSGAPGQRVTISC TGSRSNIGAGYDVH WYQQLPGTAPKLLIY GNNKR ADI-21089 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSGPI FGGGTKVTVL (“LC”) amino acid sequence

Ab 334 667 EVQLLESGGGLVKPGGSLRLSCAASGFTSG FTFSDFYMS WIRLTPGKGLEWIS YISTH ADI-21090 Heavy chain variable region

STSTNYADSVRG RFIISRDDARNSLFLQMNSLRAEDTAVYYC AGYYYGSGSYFFDH (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 334 668 ETTLTQSPATLSVSPGERATLSC RASQSVSSNVA WYQQKPGQAPRLLIY SASSRDTG ADI-21090 Light chain variable region

IPVRFSGSGSGTEFTLSISSLQSEDFAVYYC QQYSDWPT FGQGTKVEIK (“LC”) amino acid sequence

Ab 335 669 QVQLVQSGAEVKKPGESLRISCQYSA YGFSTYWIS WVRQLPGKGLEWMG RIDPSD ADI-21091 Heavy chain variable region

SHTTYSPSFQG HVTLSADKSISTVYLQWSSLKASDTAMYYC ARHQEYSGSDLDS WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 335 670 QPVLTQPPSVSAAPGQRVTISC SGTRSNIGYNFVS WYQQLPGTAPKLLIY DNNKRPS ADI-21091 Light chain variable region

GIPDRFSGSKSGTSATLAITGLQTGDEADYYC GTWDSSLSAL FGGGTKVTVL (“LC”) amino acid sequence

Ab 336 671 EVQLLESGGGVVQPGRSLRLSCVASG FTFSTYGVH WVRQAPGKGLEWVA VISYDG ADI-22756 Heavy chain variable region

ANKDYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKMITRVLPGGFDR (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 336 672 EIVMTQSPGTLSLSPGERATLSC RASQSVSSAYLA WYQQKPGQAPRLLIY DASRRAT ADI-22756 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSRFT FGQGTKVEIK (“LC”) amino acid sequence

Ab 337 673 EVQLLESGAEVKKPGASVKVSCKASG YTFSNYGIS WVRQAPGQGLEWMG WISVY ADI-22757 Heavy chain variable region

NGNTEYAQKFQG RLTMTTDTSTSTAYMELRSLRSDDTAVYYC ARDPPAVAASFMD (“HC”) amino acid sequence

V WGQGTTVTVSS

Ab 337 674 EIVLTQSPLSLPVTLGQPASISC RSSQSLVHSEGNTYLS WFQQRPGQSPRRLIY KVSN ADI-22757 Light chain variable region

RDS GVPDRFSGSGSGTDFTLKISRVEAEDVGLYFC MQGTHWPPT FGGGTKVEIK (“LC”) amino acid sequence

Ab 338 675 QVQLVESGGGLVKPGGSLRLSCAASG FSISSYSMN WVRQAPGKGLEWVS SISGSSS ADI-22758 Heavy chain variable region

YIYYGDSVKG RFTISRDNARNSLYLQMNSLRAEDTAVYYC ARGDIAAAGTITYYFAH (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 338 676 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLTGTAPKLLIF GNNNR ADI-22758 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGAV FGGGTQLTVL (“LC”) amino acid sequence

Ab 339 677 EVQLLESGGGLVKPGGSLRLSCAASG FSFSSYTMN WVRQAPGKGLEWVS SITGGSS ADI-22759 Heavy chain variable region

YIDYAGSLKG RFTISRDNAKNSLYLQMNSLRVEDTAVYYC ARDFPNIAVGGKTLDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 339 678 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WFQQLPGTAPKLLIY VNNNR ADI-22759 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDRLSAVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 340 679 EVQLVESGGGLVQPGRSLRLSCVASG FTFDDYAMH WVRQAPGKGLEWVS GINW ADI-22760 Heavy chain variable region

NSGGIGYADSVKG RFTISRDNTKNSLYLQMNSLRAEDTALYYC AKDGSALMGYGVE (“HC”) amino acid sequence

V WGQGTTVTVSS

Ab 340 680 SYELTQPPSASGTPGQRVTISC SGSNSNIGNNYVY WYQQLPGTAPKLLIY RNNQWP ADI-22760 Light chain variable region

S GVPDRFSASKSGTSASLAISGLRSEDEADYYC ASWDDSLSALV FGGGTKLTVL (“LC”) amino acid sequence

Ab 341 681 EVQLVESGPGLVKPSQTLSLTCAISG DSVSSNSVAWN WIRQSPSRGLEWLG RTYYQ ADI-22762 Heavy chain variable region

SKWYNDYAVSVKS RISVNPDTSKNQFSLQLNSLTPEDTAVYYC VRGCSWGFGWYF (“HC”) amino acid sequence

DL WGRGTLVTVSS

Ab 341 682 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAIYDVH WYQQFPGTAPKLLIY GNTNRP ADI-22762 Light chain variable region

S GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 342 683 EVQLVESGGGLIQPGGSLRLSCAASG FTFSTYEMN WVRQAPGKGLEWVS SISTSGS ADI-22763 Heavy chain variable region

TKDYAGSVKG RFTVSRDNAKNSLYLQMNSLRAEDTAIYYC ARVYYYDSSGYYLALFD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 342 684 EIVLTQSPSSLSASVGDRVTITC RASQSIASYLN WYQQKPGKAPKLLIY AASSLRS GVP ADI-22763 Light chain variable region

SRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPSLT FGGGTKLEIK (“LC”) amino acid sequence

Ab 343 685 QVQLVESGPGLVRPSGTLSLTCAVSGG SISGKNWWS WVRQPPGKGLEWIG EIDHS ADI-22764 Heavy chain variable region

GSTNYNPSLKS RVTISVDKSKNQFSLKLSSVTAADTAVYYC ARTGLYDSSGYYLYYFN (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 343 686 EIVMTQSPSSLSASVGDRVTISC RASQTIASYVN WYQQRPGKAPNLLIF AASNLQT G ADI-22764 Light chain variable region

VPSRFRGSGSGTVFTLTISSLQPEDFATYYC QQSYSTPRT FGQGTKVDIK (“LC”) amino acid sequence

Ab 344 687 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-22765 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDRGDGYNYDY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 344 688 QPVLTQPPSVSGAPGQRVTISCT GSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-22765 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSVV GGGGTKVTVL (“LC”) amino acid sequence

Ab 345 689 EVQLVESGGGLVQPGRSLRLSCAASG FTFDDYAMH WVRQAPGKGLEWVS GISW ADI-22766 Heavy chain variable region

NSGSIGYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTALYYC AKDGRFSLSHTYYF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 345 690 QPVLTQPPSASGSPGQSVTISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY EVSKR ADI-22766 Light chain variable region

PS GVPNRFSGSKSGNTASLIVSGLQAEDEADYYC SSYAGSNNLYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 346 691 QVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-22767 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREANWGVAFDI WGQ (“HC”) amino acid sequence

GTMVTVSS

Ab 346 692 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-22767 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSYV FGIGTKVTVL (“LC”) amino acid sequence

Ab 347 693 EVQLVESGGGLVQPGGSLRLSCAASG FTFSSYEMN WVRQAPGKGLEWVS YISSSG ADI-22768 Heavy chain variable region

STIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AKSYIYDSSGYYLYYFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 347 694 EIVMTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIY AASSLQS GV ADI-22768 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPGT FGQGTKVDIK (“LC”) amino acid sequence

Ab 348 695 QVQLVQSGGGLVQPGGSLRLSCAASG FTFSDHYMD WVRQAPGKGLEWVG RTRN ADI-22769 Heavy chain variable region

KANSYTTEYAASVKG RFTISRDDSKNSLYLQMNSLKTEDTAVYYC ARVGYYYYYGM (“HC”) amino acid sequence

DV WGQGTTVTVSS

Ab 348 696 SYVLTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY QDSKRPS GI ADI-22769 Light chain variable region

PERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTPL FGGGTKVTVL (“LC”) amino acid sequence

Ab 349 697 QVTLKESGPALVKPTQTLTLTCTFSG FSLSTSGMCVS WIRQPPGKALEWLA LIDWD ADI-22770 Heavy chain variable region

DDKYYSTSLKT RLTISKDTSKNQVVLTMTNMDPVDTATYYC ARSPGRAVAGTDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 349 698 SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY QDSKRPS GI ADI-22770 Light chain variable region

PERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTAVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 350 699 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-22771 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDYSSGWYYFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 350 700 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-22771 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV FGGGTKLTVL (“LC”) amino acid sequence

Ab 351 701 EVQLVESGGGVVQPGRSLRLSCAASG FTFSSYAMH WVRQAPGKGLEWVA VISYD ADI-22772 Heavy chain variable region

GSNKYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARAVEQQLFIWYYG (“HC”) amino acid sequence

MDV WGQGTTVTVSS

Ab 351 702 SYELIQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY QDSKRPSGI ADI-22772 Light chain variable region

PERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTDVV FGGGTQLTVL (“LC”) amino acid sequence

Ab 352 703 QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYGIS WVRQAPGQGLEWMG WISAY ADI-22773 Heavy chain variable region

NGNTNYAQKLQG RVTMTTDTSTSTAYMELRSLRSDDTAVYYC ARESALSRDGYNY (“HC”) amino acid sequence

GDVDY WGQGTLVTVSS

Ab 352 704 ETTLTQSPLSLPVTLGQPASISC RSSQSLVYSDGNTYLN WFQQRPGQSPRRLIY KVSN ADI-22773 Light chain variable region

RDS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQGTHWPPT FGQGTKLEIK (“LC”) amino acid sequence

Ab 353 705 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-22774 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREGASGYNYRYYFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 353 706 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQFPGAAPKLLIY GNNN ADI-22774 Light chain variable region

RPS GVPDRFSGSKSGTSASLAITGLQADDEADYYC QSYDSSLSGYVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 354 707 EVQLLESGGGVVQPGRSLRLSCAASG FTFSDYGMH WVRQAPGKGLEWVA VIWYD ADI-22775 Heavy chain variable region

GSYKYYADSVKG RFTISRDNSKNTLFLQMNSLRAEDTAVYYC ARESLQTHDAFDI W (“HC”) amino acid sequence

GQGTMVTVSS

Ab 354 708 DIQMTQSPSSLSASVGDRVTITC RASQGISNSLA WYQQKPGKAPKLLLY AASRLES G ADI-22775 Light chain variable region

VPSRFSGSGSGTDYTLTINSLQPEDFATYFC QQYYSTLTWT FGQGTKVDIK (“LC”) amino acid sequence

Ab 355 709 EVQLLESGGGLVKPGGSLRLSCAASG FTFSDYYMS WIRQAPGKGLEWVS YISSSGST ADI-22776 Heavy chain variable region

IYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREIGGSYTGGAFDI WG (“HC”) amino acid sequence

QGTMVTVSS

Ab 355 710 SYELTQPPSVSVAPGQTARITC GGNNIGSKSVH WYQQKPGQAPVLVVY DDSDRPS ADI-22776 Light chain variable region

GIPERFSGSNSGNTATLTISRVEAGDEADYYC QVWDSSSDHVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 356 711 QVQLVQSGAEVKRPGASVKVSCKASE YTFNFHDIN WVRQAPGQGLEWMG WMN ADI-22777 Heavy chain variable region

PKSGNTGYAQKFQG RVTMTRDTSKNTAYLELSSLRSEDTAVYYCA RGYGTSWSSDS (“HC”) amino acid sequence

W WGQGTLVTVSS

Ab 356 712 SYELTQLPSVSVSPGQTARITC SGDALSKQFVY WYQQKPGLAPMLVIY KDTNRPS W ADI-22777 Light chain variable region

IPERFSGSGSGTTATLTISEVQAEDEADYYC QSVDNSGTYGWVF GGGTKVTVL (“LC”) amino acid sequence

Ab 357 713 EVQLVESGPGLVKPSETLSLTCTVSG GSINSYSWT WIRQPPGKGLEWLG SFDYSGSN ADI-22778 Heavy chain variable region

TYNPSLKS RVTIAVDTSKNQFSLKLTSATAADTAVYYC ARAPVYDSSGYYLYYFDN W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 357 714 DIQMTQSPSSLSASVGDRVTITC RASQSIASYLN WYQQKPGKAPKLLIF AASNLHS G ADI-22778 Light chain variable region

VPSRFSGSGSGTTFTLTISSLQPEDFATYYC QQSYSIRFFT FGPGTKLEIK (“LC”) amino acid sequence

Ab 358 715 QVQLQQWGAGLLKPSETLSLTCAVYG GSFSDYSWT WIRQPPGKGLEWIG EISHTGI ADI-22779 Heavy chain variable region

TNYNPSLKS RVNISVDTSKNQFSLKLSSVTAADTAVYYC ARADAYDSSGYYVYYFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 358 716 DIQVTQSPPSLSASVGDRVTITC RASQTIASYLN WYHQKPGKAPELLIY AASSLQS GV ADI-22779 Light chain variable region

PSRFSGSGSGTAFTLTISSLQPEDFATYYC QQSYSAPPS FGQGTKVEIK (“LC”) amino acid sequence

Ab 359 717 EVQLVESGPTLVKPTQTLTLICTFSG FSLSTSGVGVG WIRQPPGKALEWLA LIYWDD ADI-22780 Heavy chain variable region

DKRYSPSLKS RLTITKDTSKNQVVLTMTNMDPVDTATYYC AHRGRQYSYGYYYFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 359 718 QSVLIQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQHPGKAPKLMIY DVSNR ADI-22780 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSTLDV FGTGTKVTVL (“LC”) amino acid sequence

Ab 360 719 EVQLVESGGGLVQPGGSLRLSCAASG FTFSSYEMN WVRQAPGKGLEWVS YISSSG ADI-22781 Heavy chain variable region

STIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARGGAVAGTRTGGFDI (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 360 720 SYELTQPPSVSVSPGQTARITC SGDALPKQYAY WYQQKPGQAPVLVIY KDSERPS GI ADI-22781 Light chain variable region

PERFSGSSSGTTVTLTISGVQAEDEADYYC QSADSSGTYQV FGGGTKLTVL (“LC”) amino acid sequence

Ab 361 721 EVQLVESGGGLVKPGGSLRLSCAASG FIFSDYYMS WIRQAPGKGLEWVS NISGGSS ADI-24792 Heavy chain variable region

FTNYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDLGYCSSNSCLDAF (“HC”) amino acid sequence

DI WGQGTTVTVSS

Ab 361 722 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNTNR ADI-24792 Light chain variable region

PS GVPDRFSGSRSGTSASLAITGLQAEDEADYYC QSYDSSLSGSL FGGGTKVTVL (“LC”) amino acid sequence

Ab 362 723 QVQLVQSGAEVKKPGESLKISCKGSG YSFTSYWIG WVRQMPGKGLEWMG IIYPGD ADI-24793 Heavy chain variable region

SDTRYSPSFQG QVTISADKSISTAYLQWSSLKASDTAMFYC VMGSYSYYFDY WGQG (“HC”) amino acid sequence

TLVTVSS

Ab 362 724 NFMLTQPHSVSESPGKTVTISC TRSSGSIASNYVQ WYQQRPGSAPTTVIY EDNLRPS ADI-24793 Light chain variable region

GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDSSNQV FGGGTKLTVL (“LC”) amino acid sequence

Ab 363 725 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24795 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARVGYSSSSGAFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 363 726 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24795 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV FGGGTKVTVL (“LC”) amino acid sequence

Ab 364 727 QVQLVQSGGGVVQPGRSLRLSCAASG FTFSSYGMH WVRQAPGKGLEWVA VIWY ADI-24796 Heavy chain variable region

DGSNKYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARTAYGSGSYPIYY (“HC”) amino acid sequence

YYYMDV WGKGTTVTVSS

Ab 364 728 SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY QDSKRPS GI ADI-24796 Light chain variable region

PERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 365 729 EVQLLESGPGLVKPSETLSLTCTVSG GSISSYYWS WIRQPPGKGLEWIG YIYYSGSTN ADI-24798 Heavy chain variable region

YNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARILGHCSGGSCYRIIDY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 365 730 QPVLTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY QDSKRPS G ADI-24798 Light chain variable region

IPERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTGV FGGGTKLTVL (“LC”) amino acid sequence

Ab 366 731 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24799 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREGRDGYNYYFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 366 732 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24799 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV FGGGTKLTVL (“LC”) amino acid sequence

Ab 367 733 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24800 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARVRGGYSYGYGMDV (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 367 734 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGFDVH WYQQLPGTAPKLLIY GNSNR ADI-24800 Light chain variable region

PS GVPDQFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 368 735 QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYGIS WVRQAPGQGLEWMG WISAY ADI-24801 Heavy chain variable region

NGNTNYAQKLQG RVTMTTDTSTSTAYMELRSLRSDDTAVYYC ARVTARTFGGIRK (“HC”) amino acid sequence

GYYYGMDV WGQGTTVTVSS

Ab 368 736 SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY QDSKRPS GI ADI-24801 Light chain variable region

PERFSGSNSGNTATLTISGTQVMDEADYYC QAWDSSTVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 369 737 EVQLLESGGGLVLPGGSLRLSCAASGF TFSSYAMS WVRQAPGKGLEWVS AISGSGI ADI-24803 Heavy chain variable region

YTYYADSVKG RFTISRDNSKNTLYLQMSSLRAEDTAVYYC AKGSLGMAYSAFDI WG (“HC”) amino acid sequence

LGTTVTVSS

Ab 369 738 DIQLTQSPGTLSLSSGERATLSC RASQSVSSNYLA WYQQKPGQPPRLLIY GASSRAT ADI-24803 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPLT FGGGTKVDIK (“LC”) amino acid sequence

Ab 370 739 QVQLVQSGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSS ADI-24805 Heavy chain variable region

SYIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREGYSSSSGYYYYMD (“HC”) amino acid sequence

V WGKGTTVTVSS

Ab 370 740 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24805 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV FGIGTKVTVL (“LC”) amino acid sequence

Ab 371 741 EVQLVESGPGLVKPSETLSLICTVSG GSISSSSYYWG WIRQPPGKGLEWIG SIYYSGS ADI-24807 Heavy chain variable region

TYYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARHVNPYYDSSGTPYYYYG (“HC”) amino acid sequence

MDV WGQGTTVTVSS

Ab 371 742 SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY QDSKRPS GI ADI-24807 Light chain variable region

PERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSGTVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 372 743 QVQLVQSGAEVKKPGASVKVSCKASG YTFTGYYMH WVRQAPGQGLEWMG WIN ADI-24808 Heavy chain variable region

PNSGGTNYAQKFQG WVTMTRDTSISTAYMELSRLRSDDTAVYYC ARGDPAANDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 372 744 QPVLTQPPSASGSPGQSVTISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY EVSKR ADI-24808 Light chain variable region

PS GVPDRFSGSKSGNTASLIVSGLQAEDEADYYC SSYAGSNNVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 373 745 QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYDIN WVRQATGQGLEWMG WMN ADI-24811 Heavy chain variable region

PNSGNTGYAQKFQG RVTMTRNTSISTAYMELSSLRSEDTAVYYC ARGLPGQWLEY (“HC”) amino acid sequence

YFDY WGQGTLVTVSS

Ab 373 746 SYVLTQPPSVSVAPGKTARITC GGNNIGSKSVH WYQQKPGQAPVLVIY YDSDRPS GI ADI-24811 Light chain variable region

PERFSGSNSGNTATLTISRVEAGDEADYYC QVWDSSSDHPV FGGGTKVTVL (“LC”) amino acid sequence

Ab 374 747 EVQLVESGGGLVQPGGSLRLSCAASG FSFSTYAMS WVRQAPGKGLEWVS AISGGG ADI-24812 Heavy chain variable region

GSTYYADSVKG RFTISRDNSKNTLYLQVNSLRAEDTAVYYC ARGGYCSSDSCYPFDF (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 374 748 QPVLTQPPSVSVSPGQTAMITC SGDALPKQYAY WYQQKPGQAPVLVIY KDSERPS ADI-24812 Light chain variable region

GIPERFSGSSSGTTVTLTISGVQAEDEADYYC QSADNSGSYAV FGGGTQLTVL (“LC”) amino acid sequence

Ab 375 749 EVQLLESGGGLVQPGRSLRLSCAASG FTFDDYAMH WVRQAPGKGLEWVS GISWN ADI-24813 Heavy chain variable region

SGSIGYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTALYYC AKDGDSSSWRDSNF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 375 750 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24813 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 376 751 EVQLLESGGGVVQPGRSLRLSCAASG FTFNSYTMH WVRQAPGKGLEWVA VISYD ADI-24814 Heavy chain variable region

GSNKYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARGRPYDFWSGYYT (“HC”) amino acid sequence

DYYYYMDV WGKGTTVTVSS

Ab 376 752 EIVLTQSPGTLSLSPGERATLSC RASQSVYSNYLA WYQQKPGQAPRLLIY GASSRAT ADI-24814 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQCGSSWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 377 753 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24815 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREGYSSSSGYYYMDV (“HC”) amino acid sequence

WGKGTTVTVSS

Ab 377 754 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24815 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV FGIGTKVTVL (“LC”) amino acid sequence

Ab 378 755 QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYDIN WVRQATGQGLEWMG WMN ADI-24816 Heavy chain variable region

PNSGNTGYAQKFQG RVTMTRNTSISTAYMELSSLRSEDTAVYYC ARGIPGYYYYGM (“HC”) amino acid sequence

DV WGQGTTVTVSS

Ab 378 756 SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY QDSKRPS GI ADI-24816 Light chain variable region

PERFSGSNSGNTATLTISGTQAMDEADYY CQAWDSSTYV FGIGTKVTVL (“LC”) amino acid sequence

Ab 379 757 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24817 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDSMALLYSNYWFDP (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 379 758 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24817 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV FGGGTKLTVL (“LC”) amino acid sequence

Ab 380 759 QVQLVQSGAEVKKPGASVKVSCKASG YTFTGYYMH WVRQAPGQGLEWMG WIN ADI-24818 Heavy chain variable region

PNSGGTNYAQKFQG RVTMTRDTSISTAYMELSRLRSDDTAVYYC ARGGTGVEFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 380 760 QPVLTQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY DVSNR ADI-24818 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSTLV FGGGTQLTVL (“LC”) amino acid sequence

Ab 381 761 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24819 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARESGSGWYYFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 381 762 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24819 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDGSLSGV FGGGTKVTVL (“LC”) amino acid sequence

Ab 382 763 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYTIS WVRQAPGQGLEWMG RIIPILG ADI-24820 Heavy chain variable region

IANYAQKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYC ARDPPYLRAFDI WGQGT (“HC”) amino acid sequence

TVTVSS

Ab 382 764 ETTLIQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIY AASSLQS GV ADI-24820 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPLLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 383 765 EVQLVESGGGLVQPGRSLRLSCAASG FTFDDYAMH WVRQAPGKGLEWVS GISW ADI-24821 Heavy chain variable region

NSGSIGYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTALYYC AKDKDNWNYDAF (“HC”) amino acid sequence

DI WGQGTMVTVSS

Ab 383 766 SYELTQPPSASGTPGQRVTISC SGSSSNIGSNTVN WYQQLPGTAPKLLIY SNNQRPS ADI-24821 Light chain variable region

GVPDRFSGSKSGTSASLAISGLQSEDEADYYC AAWDDSLNGPV FGGGTKLTVL (“LC”) amino acid sequence

Ab 384 767 QVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24822 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDSGLGSRGDAFDI W (“HC”) amino acid sequence

GQGTMVTVSS

Ab 384 768 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24822 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYV FGIGTKVTVL (“LC”) amino acid sequence

Ab 385 769 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24823 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREGDYYGSGRPFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 385 770 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24823 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 386 771 QVQLQESGPGLVKPSETLSLTCTVSG GSISSYYWS WIRQPPGKGLEWIG YIYYSGST ADI-24824 Heavy chain variable region

NYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC AISLYGDYRTDAFDI WGQGT (“HC”) amino acid sequence

TVTVSS

Ab 386 772 EIVLTQSPSSFSASTGDRVTITC RASQGISSYLA WYQQKPGKAPKLLIY AASTLQS GVP ADI-24824 Light chain variable region

SRFSGSGSGTDFTLTISCLQSEDFATYYC QQYYSYPL FGGGTKVEIK (“LC”) amino acid sequence

Ab 387 773 QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYDIN WVRQATGQGLEWMG WMN ADI-24825 Heavy chain variable region

PNSGNTGYAQKFQG RVTMTRNTSISTAYMELSSLRSEDTAVYYC SSVGGYYYYGM (“HC”) amino acid sequence

DV WGQGTTVTVSS

Ab 387 774 EIVMTQSPLSLPVTPGEPASISC RSSQSLLHSNGYNYLD WYLQKPGQSPQLLIY LGSN ADI-24825 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTLYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 388 775 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24826 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDRGYGSGALDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 388 776 QPVLTQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY DVSNR ADI-24826 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSTVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 389 777 EVQLVESGGGLVQPGGSLRLSCAASG FTVSSNYMS WVRQAPGKGLEWVS VIYSDG ADI-24827 Heavy chain variable region

STYYADSVKG RFTISRHNSKNTLYLQMNSLRAEDTAVYYCA RCSTYGDYIDWYFDL (“HC”) amino acid sequence

WGRGTLVTVSS

Ab 389 778 ETTLTQSPATLSVSPGERATLSC RASQSVSSNLA WYQQKPGQAPRLLIY GASTRAT G ADI-24827 Light chain variable region

IPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPLS FGGGTKLEIK (“LC”) amino acid sequence

Ab 390 779 EVQLVESGGGLVKPGGSLRLACAASG FSFRSYRMN WVRQAPGKGLEWVS SISSSSS ADI-24828 Heavy chain variable region

YIDYADSVKG RFTISRDNAKNTVYLQVNSLRAEDTAVYYC ARDGRTIFGVVIDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 390 780 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNNNR ADI-24828 Light chain variable region

PS GVPDRFSGSKSGTSASLVITGLQAEDEADYYC QSYDSSLSVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 391 781 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24829 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARGFHYYGSGSHDAFDI (“HC”) amino acid sequence

WGQGTMVTVSS

Ab 391 782 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24829 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGV FGGGTKLTVL (“LC”) amino acid sequence

Ab 392 783 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYAIS WVRQAPGQGLEWMG GIIPIF ADI-24830 Heavy chain variable region

GTANYAQKFQG RVTITADESTSTAYMELSSLRSEDTAVYYC ARGGSMVRGLGFDP (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 392 784 DIQLTQSPLSLPVTPGEPASISC RSSQSLLHSNGYNYLD WYLQKPGQSPQLLIY LGSN ADI-24830 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPLT FGGGTKLEIK (“LC”) amino acid sequence

Ab 393 785 QVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24831 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARVPSDFWSGYYNDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 393 786 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24831 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 394 787 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISASSS ADI-24832 Heavy chain variable region

YIFYSDLVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARAGYYYGSGSYYVDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 394 788 QSVLTQPPSVSGAPGQRVAISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24832 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYGSSLSGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 395 789 QVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24833 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARALTYYYDSSGHGADY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 395 790 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24833 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 396 791 QVQLVQSGGGLVQPGGSLRLSCAASG FTFSSYAMS WVRQAPGKGLEWVS TISGS ADI-24834 Heavy chain variable region

GGSTYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC ATWKRWGSGYYYS (“HC”) amino acid sequence

YMDV WGKGTTVTVSS

Ab 396 792 DIQLTQSPSTLSASVGDRVTITC RASQSISSWLA WYQQKPGKAPKLLIY DAFSLES GV ADI-24834 Light chain variable region

PSRFSGSGSGTEFTLTISSLQPDDFATYYC QQYNSYSVT FGGGTKVEIK (“LC”) amino acid sequence

Ab 397 793 EVQLVESGGGLVKPGGSLRLSCAASG FPFSTSSMN WVRQAPGKGLEWVS SISSSSS ADI-24835 Heavy chain variable region

YIDYADSVKG RFTISRDNAKNSLYLQMNSLRAGDTAVYYC ARVPRSDWYYFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 397 794 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKFLIY DNKYR ADI-24835 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 398 795 EVQLLESGGGLVQPGRSLRLSCAASG FTFDDYAMH WVRQAPGKGLEWVS GISWN ADI-24836 Heavy chain variable region

SGSIGYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTALYYC AKDLRGGTYYYYGM (“HC”) amino acid sequence

DV WGQGTTVTVSS

Ab 398 796 DIRVTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIY AASSLQS GV ADI-24836 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPPT FGGGTKVEIK (“LC”) amino acid sequence

Ab 399 797 QVQLQESGPGLVKPSETLSLTCTVSG GSISSYYWS WIRQPPGKGLEWIG YIYYSGST ADI-24837 Heavy chain variable region

NYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARAIYYYDSSGYYYVGDAFDI (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 399 798 QSVLTQPPSVSAAPGQKVTISCS GSSSNIGNNYVS WYQQLPGTAPKLLIY ENNKRPS ADI-24837 Light chain variable region

GIPDRFSGSKSGTSATLGITGLQTGDEADYYC GTWDSSLSAGV FGGGTKLTVL (“LC”) amino acid sequence

Ab 400 799 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24838 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARQGVGTVTTWNYYYY (“HC”) amino acid sequence

YMDV WGKGTTVTVSS

Ab 400 800 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24838 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 401 801 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24839 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARVLVATAYGNAFDI W (“HC”) amino acid sequence

GQGTMVTVSS

Ab 401 802 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24839 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLTVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 402 803 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24840 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDQVYSYGYYFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 402 804 QSVLAQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24840 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSHVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 403 805 QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYAMH WVRQAPGQRLEWMG WIN ADI-24841 Heavy chain variable region

AGNGNTKYSQKFQG RVTITRDTSASTAYMELSSLRSEDTAVYYC ARDGFPTNYDFW (“HC”) amino acid sequence

SGYSDDAFD IWGQGTMVTVSS

Ab 403 806 DIVMTQSPATLSVSPGERATLSC RASQSVSSNLA WYQQKPGQAPRLLIY GASTRAT ADI-24841 Light chain variable region

GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPPLT FGQGTKVDIK (“LC”) amino acid sequence

Ab 404 807 QVQLVQSGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSS ADI-24842 Heavy chain variable region

SYIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARVPPHDYGGYYFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 404 808 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY RNSNR ADI-24842 Light chain variable region

PS GVPDRFSGSKSGTSASLAIIGLQAEDEADYYC QSYDSSLSVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 405 809 EVQLVESGPGLVKPSQTLSLTCTVSG GSISSGDYYWS WIRQPPGKGLEWIG YIYYSG ADI-24843 Heavy chain variable region

STYYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARESIVGAVDY WGQGTL (“HC”) amino acid sequence

VTVSS

Ab 405 810 DIQMTQSPDSLAVSLGERATINC KSSQSVLYSSNNKNYLA WYQQKPGQPPKLLIY W ADI-24843 Light chain variable region

ASTRES GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC QQYYSTPHT FGQGTKLEIK (“LC”) amino acid sequence

Ab 406 811 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24845 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDYCSGGSCYLAAFDI (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 406 812 QPVLTQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY EVSNR ADI-24845 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSTPVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 407 813 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24846 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDDGILWLDY WGQG (“HC”) amino acid sequence

TLVTVSS

Ab 407 814 QPGLTQPPSASGTPGQRVTISC SGSSSNIGSNYVY WYQQLPGTAPKLLIY RNNQRPS ADI-24846 Light chain variable region

GVPDRFSGSKSGTSASLAISGLRSEDEADYYC AAWDDSLSGQV FGGGTKLTVL (“LC”) amino acid sequence

Ab 408 815 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSN ADI-24847 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDRIAAYTFDY WGQG (“HC”) amino acid sequence

TLVTVSS

Ab 408 816 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24847 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLPYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 409 817 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24848 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDTVVAGIYFDY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 409 818 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24848 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 410 819 QVQLVQSGGVVVQPGGSLRLSCAASG FTFDDYTMH WVRQAPGKGLEWVS LIGW ADI-24849 Heavy chain variable region

DGGSTYYADSVKG RFTISRDNSKYSLYLQMNSLRTEDTALYYC AKDLGSSSGYFLGR (“HC”) amino acid sequence

DYYGMDV WGQGTTVTVSS

Ab 410 820 DIQLTQSPSSLSASVGDRVTITC QASQDISNYLN WYQQKPGKAPKLLIY DASNLET G ADI-24849 Light chain variable region

VPSRFSGSGSGTDFTFTISSLQPEDIATYYC QQYNNLPT FGGGTKLEIK (“LC”) amino acid sequence

Ab 411 821 QVQLVQSGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSS ADI-24850 Heavy chain variable region

SYIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREDYGDYYYYYMDV (“HC”) amino acid sequence

WGKGTTVTVSS

Ab 411 822 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24850 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 412 823 QVQLVQSGAEVKKPGASVKVSCKASG YTFTGYYMH WVRQAPGQGLEWMG WIN ADI-24851 Heavy chain variable region

PNSGGTNYAQKFQG RVTMTRDTSISTAYMELSRLRSDDTAVYYC ARAYELELDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 412 824 QSVLIQPPSASGSPGQSVTISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY EVSKR ADI-24851 Light chain variable region

PS GVPDRFSGSKSGNTASLIVSGLQAEDEADYYC SSYAGSNNVV TGGGTKLTVL (“LC”) amino acid sequence

Ab 413 825 QVQLVESGAEVKKPGASVKVSCKASG YTFTSYAIH WVRQAPGQRLEWMG WINAG ADI-24852 Heavy chain variable region

NGNTKYSQKFQG RVTITRDTSASTAYMELSSLRSEDTAVYYC ASEESGYFDY WGQG (“HC”) amino acid sequence

TLVTVSS

Ab 413 826 SYELMQPPSVPVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY QDRKRPS ADI-24852 Light chain variable region

GIPERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 414 827 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24854 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDRRFGELFYFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 414 828 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24854 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGNWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 415 829 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24855 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARRYCTNGVCYDAFDI (“HC”) amino acid sequence

WGQGTMVTVSS

Ab 415 830 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24855 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 416 831 QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYGIS WVRQAPGQGLEWMG WISAY ADI-24856 Heavy chain variable region

NGNTNYAQKLQG RVTMTTDTSTSTAYMELRSLRSDDTAVYYC ARAGIVVVPKYYYY (“HC”) amino acid sequence

MDV WGKGTTVTVSS

Ab 416 832 DIVMTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLIY GASSRAT ADI-24856 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPMYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 417 833 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24857 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREGYYYGSGSYLDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 417 834 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24857 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 418 835 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24858 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARGGYSYGYSFDY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 418 836 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24858 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 419 837 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-24859 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDGSPINWVSPFPFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 419 838 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24859 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV FGGGTQLTVL (“LC”) amino acid sequence

Ab 420 839 EVQLLESGGGLVKPGGSLRLSCAASG LTFSDYYMS WIRQAPGKGLEWVS YISGGSS ADI-24860 Heavy chain variable region

YSNYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARGYCSGSSCYEAFDI (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 420 840 SYVLTQPPSVSGAPGQRVTISC TGSSSNIGAGFDVH WYQQLPGTAPKLLIY GNSDRP ADI-24860 Light chain variable region

S GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 421 841 QVQLVQSGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISGGS ADI-24861 Heavy chain variable region

SYIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREAYYYDSSGLKWFD (“HC”) amino acid sequence

PW GQGTLVTVSS

Ab 421 842 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24861 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 422 843 EVQLLESGPGLVKPSQTLSLTCTVSG GSISSGGYYWS WIRQHPGKGLEWIG YIYYSG ADI-24862 Heavy chain variable region

STYYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARLEIGDGSGSYLHWYFD (“HC”) amino acid sequence

L WGRGTLVTVSS

Ab 422 844 SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY QDSKRPS GI ADI-24862 Light chain variable region

PERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTAV FGGGTKLTVL (“LC”) amino acid sequence

Ab 423 845 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSRS ADI-24863 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARVGSGGSGTYGDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 423 846 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-24863 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 424 847 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-25462 Heavy chain variable region

YIYYADSVKG RFTISRHNAKNSLYLQMNSLRAEDTAVYYC ARGSSSSWFCFDY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 424 848 SYVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25462 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 425 849 GVQLVESGPGLVKPSETLSLTCTVSG GSISSYYWS WIRQPPGKGLEWIG YIYYSGSTN ADI-25467 Heavy chain variable region

YNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARGYYYDSSGYYPNDAFDI W (“HC”) amino acid sequence

GQGTMVTVSS

Ab 425 850 DIQVTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIY AASSLQS GV ADI-25467 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 426 851 QVQLVQSGAEVKKPGESLKISCKGSG YSFTSYWIG WVRQMPGKGLEWMG IIYPGD ADI-25468 Heavy chain variable region

SDTRYSPSFQG QVTISADKSISTAYLQWSSLKASDTAMYYC ARHVGQVYCSSTSCYT (“HC”) amino acid sequence

SREYYFDY WGQGTLVTVSS

Ab 426 852 SYVLTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY QDSKRPS GI ADI-25468 Light chain variable region

PERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTAVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 427 853 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-25472 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDDSSSWYYFDY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 427 854 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25472 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYV FGIGTKVTVL (“LC”) amino acid sequence

Ab 428 855 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-25478 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARLDYSNYYYYMDV WG (“HC”) amino acid sequence

KGTTVTVSS

Ab 428 856 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25478 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 429 857 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-25479 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARGGYSYGAYYYYYMD (“HC”) amino acid sequence

V WGKGTTVTVSS

Ab 429 858 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25479 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 430 859 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-25480 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARGGYSYGAYYYYYMD (“HC”) amino acid sequence

V WGKGTTVTVSS

Ab 430 860 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25480 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYWV FGGGTKVTVL (“LC”) amino acid sequence

Ab 431 861 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-25484 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARSIAVAGTGYGMDV W (“HC”) amino acid sequence

GQGTTVTVSS

Ab 431 862 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25484 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 432 863 EVQLLESGPGLVKPSQTLSLTCTVSG GSISSGGYYWS WIRQHPGKGLEWIG YIYYSG ADI-25491 Heavy chain variable region

STYYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC AREVVPAAIRAGYYFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 432 864 SYELMQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY QDSKRPS G ADI-25491 Light chain variable region

IPERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTGGV FGTGTQLTVL (“LC”) amino acid sequence

Ab 433 865 QVQLVQSGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSS ADI-25495 Heavy chain variable region

SYIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARGYCTNGVCYLDAFD (“HC”) amino acid sequence

I WGQGTTVTVSS

Ab 433 866 QSVLIQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY DVSNR ADI-25495 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSTPVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 434 867 QVQLVQSGGGLVKPGGSLRLSCAAS GFTFSSYSMN WVRQAPGKGLEWVS SISSSS ADI-25496 Heavy chain variable region

SYIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARVASEVWFFDL WGR (“HC”) amino acid sequence

GTLVTVSS

Ab 434 868 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25496 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 435 869 EVQLLESGGGLVQPGGSLRLSCAASG FTFSSYWMS WVRQAPGKGLEWVA NIKQD ADI-25497 Heavy chain variable region

GSEKYYVDSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDGLLQYDFWSGY (“HC”) amino acid sequence

YDY WGQGTLVTVSS

Ab 435 870 EIVLTQSPSSLSASVGDRVTITC RASQGISSWLA WYQQKPEKAPKSLIY AASSLQS GV ADI-25497 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYNSYPFT FGPGTKVDIK (“LC”) amino acid sequence

Ab 436 871 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYAIS WVRQAPGQGLEWMG GIIPIF ADI-25502 Heavy chain variable region

GTANYAQKFQG RVTITADESTSTAYMELSSLRSEDTAVYYC ARDHWSNPLYYYGM (“HC”) amino acid sequence

DV WGQGTTVTVSS

Ab 436 872 SYELTQPPSVSVSPGQTARITC SGDVLAKKYAR WFQQKPGQAPVLVIY KDSERPS GI ADI-25502 Light chain variable region

PERFSGSSSGTTVTLTISGAQVEDEADYYC YSAADNNLGV FGGGTQLTVL (“LC”) amino acid sequence

Ab 437 873 EVQLLESGAEVKKPGSSVKVSCKASG GTFSSYAIS WVRQAPGQGLEWMG GIIPIFG ADI-25503 Heavy chain variable region

TANYAQKFQG RVTITADESTSTAYMELSSLRSEDTAVYYC ARSRYSGSYYYYYGMDV (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 437 874 QPVLTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY QDSKRPS G ADI-25503 Light chain variable region

IPERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 438 875 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-25505 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARVVGYSGSYLDY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 438 876 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25505 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 439 877 EVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYAIS WVRQAPGQGLEWMG GIIPIFG ADI-25514 Heavy chain variable region

TANYAQKFQG RVTITADESTSTAYMELSSLRSEDTAVYYC ARSRYSGSYYYYYGMDV (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 439 878 SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY QDSKRPSGI ADI-25514 Light chain variable region

PERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTYV FGIGTKLTVL (“LC”) amino acid sequence

Ab 440 879 QVQLVQSGAEVKKPGASVKVSCKASG YTFTGYYMH WVRQAPGQGLEWMG WIN ADI-25517 Heavy chain variable region

PNSGGTNYAQKFQG RVTMTRDTSISTAYMELSRLRSDDTAVYYC ARDWAWDAFD (“HC”) amino acid sequence

I WGQGTMVTVSS

Ab 440 880 QPGLTQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY DVSN ADI-25517 Light chain variable region

RPS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSTLV FGGGTKLTVL (“LC”) amino acid sequence

Ab 441 881 EVQLVESGAEVKKPGASVKVSCKASG YTFTGYYMH WVRQAPGQGLEWMG WINP ADI-25518 Heavy chain variable region

NSGGTNYAQKFQG RVTMTRDTSISTAYMELSRLRSDDTAVYYC ARDWAWDAFDI (“HC”) amino acid sequence

WGQGTMVTVSS

Ab 441 882 QSVLIQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY DVSNR ADI-25518 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSTLV FGGGTQLTVL (“LC”) amino acid sequence

Ab 442 883 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-25524 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREWSPIVVVTNAFDI W (“HC”) amino acid sequence

GQGTMVTVSS

Ab 442 884 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25524 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGWV FGGGTKVTVL (“LC”) amino acid sequence

Ab 443 885 QVQLVQSGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSS ADI-25532 Heavy chain variable region

SYIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARGSSSSWYYFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 443 886 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25532 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSYV FGIGTKVTVL (“LC”) amino acid sequence

Ab 444 887 QVQLVQSGAEVKKPGASVKVSCKASG YTFTGYYMH WVRQAPGQGLEWMG WIN ADI-25533 Heavy chain variable region

PNSGGTNYAQKFQG WVTMTRDTSISTAYMELSRLRSDDTAVYYC ARDANWGAFD (“HC”) amino acid sequence

I WGQGTMVTVSS

Ab 444 888 QSVLIQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY DVSNR ADI-25533 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSTWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 445 889 EVQLVESGGGLVQPGGSLRLSCAASG FTFSSYAMS WVRQAPGKGLEWVS AISGSG ADI-25542 Heavy chain variable region

GSTYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKDYYYDSSGYPPYGI (“HC”) amino acid sequence

GV WGQGTTVTVSS

Ab 445 890 QTVVTQEPSFSVSPGGTVTLTC GLSSGSVSTSYYPS WYQQTPGQAPRTLIY STNTRS ADI-25542 Light chain variable region

S GVPDRFSGSILGNKAALTITGAQADDESDYYC VLYMGSGIWV FGGGTKVTVL (“LC”) amino acid sequence

Ab 446 891 EVQLLESGGGLIQPGGSLRLSCAASG FTVSSNYMS WVRQAPGKGLEWVS VIYSGGS ADI-25547 Heavy chain variable region

TYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARGGIADAFDI WGQGT (“HC”) amino acid sequence

MVTVSS

Ab 446 892 ETTLTQSPSSVSASVGDRVTITC RASQGISSWLA WYQQKPGKAPKLLIY AASSLQSG ADI-25547 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQANSFPRT FGQGTKLEIK (“LC”) amino acid sequence

Ab 447 893 EVQLVESGGGLIQPGGSLRLSCAASG FTVSSNYMS WVRQAPGKGLEWVS VIYSGG ADI-25548 Heavy chain variable region

STYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARGPQFGVSYSSGWYS (“HC”) amino acid sequence

FDY WGQGTLVTVSS

Ab 447 894 QSVLIQPRSVSGSPGQSVTISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY DVSKR ADI-25548 Light chain variable region

PS GVPDRFSGSKSGNTASLTISGLQAEDEADYY CCSYAGSYTFVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 448 895 QVQLVQSGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSS ADI-25549 Heavy chain variable region

SYIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARVSSGWYGGGAYYF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 448 896 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25549 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSALYV FGIGTKVTVL (“LC”) amino acid sequence

Ab 449 897 QVQLVQSGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSS ADI-25555 Heavy chain variable region

SYIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARQRGGIAVAGTYFDL (“HC”) amino acid sequence

WGRGTLVTVSS

Ab 449 898 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25555 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSTVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 450 899 QVQLVQSGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSS ADI-25556 Heavy chain variable region

SYIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARQRGGIAVAGTYFDL (“HC”) amino acid sequence

WGRGTLVTVSS

Ab 450 900 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25556 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSTVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 451 901 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-25557 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARGYGSGSYLDYFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 451 902 QPGLTQPPSVSGAPGQRVTISCT GSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25557 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGFYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 452 903 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-25559 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDAAAKYYFDY WGQG (“HC”) amino acid sequence

TLVTVSS

Ab 452 904 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25559 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGKV FGTGTKLTVL (“LC”) amino acid sequence

Ab 453 905 QVQLVESGGGLVKPGGSLRLSCAASG FTFSDYYMS WIRQAPGKGLEWVS YISSSSS ADI-25562 Heavy chain variable region

YTNYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARVGYSSSWYNYFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 453 906 SYVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25562 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGPV FGGGTKLTVL (“LC”) amino acid sequence

Ab 454 907 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-25565 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARIRFDYGSGSYAFDI W (“HC”) amino acid sequence

GQGTMVTVSS

Ab 454 908 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25565 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV FGGGTKLTVL (“LC”) amino acid sequence

Ab 455 909 QVQLQQWGAGLLKPSETLSLTCAVYG GSFSGYYWS WIRQPPGKGLEWIG EINHSG ADI-25567 Heavy chain variable region

STNYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARGLPRFGVVTPNWFDP (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 455 910 EIVLTQSPDSLAVSLGERATINC KSSQSVLYSSNNKNYLA WYQQKPGQPPKLLIY WA ADI-25567 Light chain variable region

STRES GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC QQYYSTPYT FGQGTKLEIK (“LC”) amino acid sequence

Ab 456 911 EVQLLESGGGLVQPGGSLRLSCAASG FTFSSYWMH WVRQAPGKGLVWVS RINSD ADI-25569 Heavy chain variable region

GSSTSYADSVKG RFTISRDNAKNTLYLQMNSLRAEDTAVYYC AREGDSSGWPGGA (“HC”) amino acid sequence

FDI WGQGTMVTVSS

Ab 456 912 SYVLTQPPSVSVSPGQAARITC SGDALPKQYAY WYQQKPGQAPVLVIY KDSERPS GI ADI-25569 Light chain variable region

PERFSGSSSGTTVTLTISGVQAEDEADYYC QSADSSGTFYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 457 913 QVQLVQSGAEVKKPGASVKVSCKASG YTFTGYYMH WVRQAPGQGLEWMG WIN ADI-25572 Heavy chain variable region

PNSGGTNYAQKFQG RVTMTRDTSISTAYMELSRLRSDDTAVYYC ARDPYSSSSYYY (“HC”) amino acid sequence

YGMDV WGQGTTVTVSS

Ab 457 914 DIVLTQSPLSLPVTPGEPASISC RSSQSLLHSNGYNYLD WYLQKPGQSPQLLIY LGSN ADI-25572 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTLYT FGQGTKVDIK (“LC”) amino acid sequence

Ab 458 915 EVQLVESGAEVKKPGASVKVSCKASG YTFTSYYMH WVRQAPGQGLEWMG IINPS ADI-25573 Heavy chain variable region

GGSTSYAQKFQG RVTMTRDTSTSTVYMELSSLRSEDTAVYYC ARGPYDSSGYCDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 458 916 SYELMQPPSVSVAPGKTARITC GGNNIGSKSVH WYQQKPGQAPVLVVY DDSDRPS ADI-25573 Light chain variable region

GTPERFSGSNSGNTATLTISRVEAGDEADYYC QVWDSSSDQV FGGGTKVTVL (“LC”) amino acid sequence

Ab 459 917 EVQLVESGAEVKKPGASVKVSCKASG YTFTSYYMH WVRQAPGQGLEWMG IINPS ADI-25575 Heavy chain variable region

GGSTSYAQKFQG RVTMTRDTSTSTVYMELSSLRSEDTAVYYC ARGPYDSSGYCDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 459 918 SYELTQPPSVSVAPGKTARITC GGNNIGSKSVH WYQQKPGQAPVLVVY DDSDRPS ADI-25575 Light chain variable region

GIPERFSGSNSGNTATLTISRVEAGDEADYYC QVWDSSSDQV FGGGTKLTVL (“LC”) amino acid sequence

Ab 460 919 EVQLVESGGGLVQPGGSLRLSCAASG FTFSSYWMH WVRQAPGKGLVWVS RINSD ADI-25576 Heavy chain variable region

GSSTSYADSVKG RFTISRDNAKNTLYLQMNSLRAEDTAVYYC ARGLYNWNHDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 460 920 NFMLTQPHSVSESPGKTVTISC TRSSGSIASNYVQ WYQQRPGSSPTTVIY EDNQRPS ADI-25576 Light chain variable region

GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDSSNVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 461 921 QVTLKESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-25577 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARYSSSLGAFDI WGQGT (“HC”) amino acid sequence

MVTVSS

Ab 461 922 QSALTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25577 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSDV FGTGTKLTVL (“LC”) amino acid sequence

Ab 462 923 QVQLVESGGGVVQPGRSLRLSCAASG FTFSSYGMH WVRQAPGKGLEWVA VIWY ADI-25587 Heavy chain variable region

DGSNKYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDSTYSEAFDI W (“HC”) amino acid sequence

GQGTMVTVSS

Ab 462 924 QSVLIQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY DVSNR ADI-25587 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSTWV FGGGTKVTVL (“LC”) amino acid sequence

Ab 463 925 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-25588 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARYSSSLGAFDI WGQGT (“HC”) amino acid sequence

TVTVSS

Ab 463 926 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25588 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYCQ SYDSSLSDV FGTGTKVTVL (“LC”) amino acid sequence

Ab 464 927 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-25595 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARYQSSSWYYFDY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 464 928 SYVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-25595 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 465 929 QVQLQESGPGLVKPSETLSLTCTVSP PSISSSSYYWG WIRQPPGKGLEWIG SIYYSGS ADI-25598 Heavy chain variable region

TYYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARPDSSGAFDI WGQGTMV (“HC”) amino acid sequence

TVSS

Ab 465 930 SYELTQPPSVSVSPGQTARITC SADALPKQYAY WYQQKPGQAPVLVIY KDSERPS GI ADI-25598 Light chain variable region

PERFSGSSSGTTVTLTISGVQAEDEADYYC QSADSSGTYVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 466 931 EVQLVQSGAEVKKPGASVRVYCKASG YTFTTYYIH WVRQAPGQGLEWMG MINPS ADI-36669 Heavy chain variable region

GGTTSYAQKFQG RLTMTGDTSTSTVYMELNYLRSEDTAVYYC TRDFIYFYGSGDGF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 466 932 EIVMTQSPSAMSASVGDRVTITC RASQGISNYLA WFQQKPGKVPKRLIY AASSLQS ADI-36669 Light chain variable region

GVPSRFSGSGSGTEFTLTITSLQPEDFATYYC LQHNSYPFT FGPGTKVEIK (“LC”) amino acid sequence

Ab 467 933 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSTYTIN WVRQAPGQGLEWMG RITPSL ADI-36670 Heavy chain variable region

GVPLSAQKFQG RITISADKSTTTAYMELSSLGSEDTAVYYC ASLNYYDTTDYYLGYSD (“HC”) amino acid sequence

S WGQGTLVTVSS

Ab 467 934 DIVLTQTPATLSVSPGERATLSC RASHSVSNNLA WYQQKPGQAPRLLIY SASTRAT GI ADI-36670 Light chain variable region

PARFSGRGSGTEFTLTISSLQPEDFAVYYC QQYNNWPPEYT FGQGTKVDIK (“LC”) amino acid sequence

Ab 468 935 EVQLLESGGGLVKPGGSLRLSCAASG FTFSGYYMT WIRQAPEKGLEWVS YISGGSTY ADI-36671 Heavy chain variable region

TNYADSVRG RFTISRDNARNSLYLQMNSLRAEDTAVYYC ARDGGYGIGPLY WGQG (“HC”) amino acid sequence

SLVTVSS

Ab 468 936 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAPFDVH WYQQLPGTAPKPLIY GNSNR ADI-36671 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLGGYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 469 937 EVQLVESGGGLVKPGGSLRLSCAASG FAFNNYYMN WVRQAPGKGLEWVS SISSAS ADI-36672 Heavy chain variable region

TYTDYADSVKG RFTISRDNAKNSLYLHLNSLRAEDTAVYYC ARDYYGSGNYYNPKPL (“HC”) amino acid sequence

DV WGQGTTVTVSS

Ab 469 938 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYRQFPGTAPELLIY GNTNR ADI-36672 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLKGV FGGGTKLTVL (“LC”) amino acid sequence

Ab 470 939 EVQLLESGGGLVKPGGSLRLSCAASG FKFRSYSMN WVRQAPGKGLEWVS SISSSSS ADI-36674 Heavy chain variable region

YVDYAGSLKG RFTISRDNAENSLYLQMNSLRAEDTAMYYC ARAGSVPVAGTYNDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 470 940 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQHLPGTAPKLLIH GNNNR ADI-36674 Light chain variable region

PA GVPDRFSGSKSGTSASLVITGLQADDEADYYC QSYDRSLSVLF GGGTKVTVL (“LC”) amino acid sequence

Ab 471 941 QVQLVQSGGGLVQPGGSLRLSCAASG FTFSSYEMN WVRQAPGKGLEWIS YISSSG ADI-36677 Heavy chain variable region

DTKYYADSVKG RFTVSRDNAKYSLYLQMDSLRAEDTAVYYC ASLYDSRGYYWVFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 471 942 DIVMTQSPSSLSASVGDRVTITC QASQDISTYLN WYQHKPGKAPNLLIY DASNLEP G ADI-36677 Light chain variable region

VPSRFSGSGSGTDFTFTISSLQPEDIATYYC LQHDNLPPT FGQGTKVDIK (“LC”) amino acid sequence

Ab 472 943 QVQLVQSGAEVKKPGESLKISCKGSG YSFRSYWIA WVRQMPGKGLEWMG TIFPG ADI-36679 Heavy chain variable region

DSDVTYSPSFQG QVTISVDKSTSTAYLQWGSLKASDTAIYYC ARRYDYIDF WGQGTL (“HC”) amino acid sequence

VTVSS

Ab 472 944 DIQMTQSPSSLSASVGDRVTITC QASQDIINHLN WYQQKPGKAPKLLIY DASNLHP ADI-36679 Light chain variable region

GVPSRFSGSGSGTYFTFTISSLQPDDFATYYC QQYDFLAHIT FGPGTKVDIK (“LC”) amino acid sequence

Ab 473 945 QVTLKESGAELRKPGESLKISCKASG YRFTNYWIG WVRQMPGKGLEWMG VIYPGD ADI-36680 Heavy chain variable region

SDTKYSPSFQG QVTMSADKSINTAYLQWSSLKASDTAIYYC VSLFGDYDYGALDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 473 946 ETTLIQSPATLSMSPGERATLSC RASQSVGRNLA WYQQKPGQAPRLLIY GASIRAT ADI-36680 Light chain variable region

GILARFSGSGSGTEYTLTISSLQPEDFAVYYC QQYHDWPSFT FGPGTKVDIK (“LC”) amino acid sequence

Ab 474 947 EVQLVESGAEVKKPGESLKISCKASG YSFTRYWIG WVRQMPGKGLEWMG IIFPGD ADI-36681 Heavy chain variable region

SDTRYCPSFEG QVTISADRSINTAYLQWSSLKASDSAMYYC VTLYTDYDYGAPDH W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 474 948 DIVLTQSPATLSVSPGERATLSC RASQSLSGDLA WYQQKPGQAPRLLIYA TSTRAT GI ADI-36681 Light chain variable region

PARFSGSGSGAEFTLTISSLQSEDFAVYYC QQYYDWPLLT FGPGTKVEIK (“LC”) amino acid sequence

Ab 475 949 EVQLVQSGAEVKKPGGSVKVSCKASG YTFSEYYMH WVRQAPGQGPEWVG RINPK ADI-41144 Heavy chain variable region

SGRTNYAQNFQG RVTMTRDRSISTVYMDLSRLRSDDTAVYYC ARWEVMDYGSGI (“HC”) amino acid sequence

YYNQDHFDY WGQGTLVTVSS

Ab 475 950 DIRVTQSPSSLSASVGDRVTITC RASQDITNYLA WFQQKPGKAPKSLMY AASTLQS G ADI-41144 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYKTYPIT FGQGTRLEIK (“LC”) amino acid sequence

Ab 476 951 QVQLVQSGPGLVKPSETLSLTCTVSA GSISNFYWS WIRQPPGKGLEWIG YIYYSGST ADI-41145 Heavy chain variable region

SYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARSRSGWSLYDY WGQGTLV (“HC”) amino acid sequence

TVSS

Ab 476 952 DIQVTQSPSSLSASVGDRVTITC RASQSISSFLN WYQQKPGKAPKLLIY VASSLQS GV ADI-41145 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYNTPLT FGGGTKVDIK (“LC”) amino acid sequence

Ab 477 953 QVQLVQSGAEVKKPGESLKISCKGSG HSFATFWIG WVRQVPGNGLELMG IINLGD ADI-41146 Heavy chain variable region

SDTKYSPSFQG QVTISADESIGTAYLQWSSLKASDTAMYYC ARVSLPHYYYYMDV W (“HC”) amino acid sequence

GKGTTVTVSS

Ab 477 954 DIVMTQSPSSVSASVGDRVTITC RASQGISTWLA WYRQKPGKAPELLIY AASRLQS G ADI-41146 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQANSFLGA FGPGTKLEIK (“LC”) amino acid sequence

Ab 478 955 EVQLVESGGGLVKPGGSLRLSCAASG FTLSGYYMS WVRQAPGKGLEWIS YISGGST ADI-41147 Heavy chain variable region

YTNYADSVNG RFTISRDNAKNSLYLQMDSLRAEDTAVYYC ARLEYGDYGPYYLGL W (“HC”) amino acid sequence

GRGTLVTVSS

Ab 478 956 QSVLTQPPSVSGAPGQRVTISCTG TSSNIGAGYDVH WYQKLPGTAPKLLIY ANNNR ADI-41147 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDTSLSAHYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 479 957 QVQLVQSGGGVVQPGRSLRLSCAASG FTFSDYGMH WVRQAPGKGLEWVA VIWF ADI-41149 Heavy chain variable region

DGSNKNYADSVKG RFTISRDNSMNTLYLQMNNLRAEDTAVYYC ARAPYSFWSGYY (“HC”) amino acid sequence

LDY WGQGSLVTVSS

Ab 479 958 DIVMTQSPATLSVSPGERATLSC RASQSISSNLA WYQQKSGQAPRLLIY GASTRAT G ADI-41149 Light chain variable region

IPARFSGSGSGTEFTLTISSLQSEDFAVYSC QQYSKWPQT FGQGTKVEIK (“LC”) amino acid sequence

Ab 480 959 EVQLVESGGGLVKPGGSLRLSCAASQ FTFSTYDMS WVRQAPGKGLEWVA SISSGS ADI-41153 Heavy chain variable region

TYIYYADSVKG RFTISRDNAKHSLFLQMKSLRAEDTALYYC ARQVLYDRGGYYLYYFD (“HC”) amino acid sequence

H WGQGTLVTVSS

Ab 480 960 DIQVTQSPSSLSASVGDRVTITC RASQTIASYLN WYQQKPGKAPNLLIY AASNLQS G ADI-41153 Light chain variable region

VPSRFSGSGSGTEFTLTINTLQPEDFATYYC QQSYNFPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 481 961 QVQLQQWGAGLSKPSETLSVTCAVYG GSLSGHYWS WFRQPPGKGLEWIG EIDHS ADI-41154 Heavy chain variable region

GSTTYNPSLKS RVTISVDTSKNQFSLKLTSVTAADTAMYYC ARATRYNYGYTFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 481 962 DIPLTQSPSSLSASVGDRVTITC RASQIISSYLN WYQQKPGKAPKLLIY AASTLQS GVP ADI-41154 Light chain variable region

SRFSGSRSGTDFTLTISSLQPEDFASYYC QQSYIIPFT FGPGTKVEIK (“LC”) amino acid sequence

Ab 482 963 QVQLQESGPGLVKPSETLSLTCTVSG GSIGNNFYYWG WIRQPPGKGLEWIG SIYYS ADI-41155 Heavy chain variable region

GTTYDNPSLKS RVTISVEPSKNQFSLKLSSVTAADTAVYHC ARRYCDSTRCYEAFDI W (“HC”) amino acid sequence

GQGTTVTVSS

Ab 482 964 SYELTQPPSASGTPGQRVTISC SGSSSNIGSNYVS WYQQLPGTAPKLLIY KNDQRPS ADI-41155 Light chain variable region

GVPDRFSGSKSGTSASLAISGLRSEDEAEYYC AAWDDSLSGFYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 483 965 QVQLVQSGGGLVQPGGSLRLSCVASG FIFSSYEMN WVRQAPGKGLEWVS YISSSG ADI-41156 Heavy chain variable region

STIYYADSVKG RFTISRDNAKNSLYLQMNSLGAEDTAVYYC ARAILYFDY WGQGTLV (“HC”) amino acid sequence

TVSS

Ab 483 966 GIRLTQSPSSLSASVGDRVTITC RASQSITNYIN WYQQKPGKAPKLLIY AISRLQS GVP ADI-41156 Light chain variable region

SRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTMYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 484 967 EVQLVESGPGLVKPSETLSLTCTVSG GSISTYYWS WIRQPPGKGLEWIG YIYYTGSTN ADI-41157 Heavy chain variable region

YNPSLKS RVTISLDTSKNQFSLKLSSVSAADTAFYYC ARSPPVPGTRSWFDP WGQGT (“HC”) amino acid sequence

LVTVSS

Ab 484 968 SPGLTQPQSAFGTPGQRVTISC FGSSSNIGRNHIY WYQQVPGTAPKLLIY RNNQRPS ADI-41157 Light chain variable region

GVPDRFFGSKFGTSASLAISGVRSEDEADYFC AAWDDSLSGPV FGGGTKLTVL (“LC”) amino acid sequence

Ab 485 969 EVQLVESGGGLVQPGGSLRLSCAASG FTFSSYNIA WVRQAPGKGLEWIS YISSSSSVI ADI-41158 Heavy chain variable region

YYADSVRG RFTISRDNAKNSLYLQMNSLRDEDTAMYYC ARAGNDYNFWSGRSSEY (“HC”) amino acid sequence

FDYWGQGTLVTVSS

Ab 485 970 DIVMTQSPATLSVSPGERATLSC RASQSVSSNLA WYQQKPGQAPRLLIY GASTRAT ADI-41158 Light chain variable region

GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYDNWPLYT FGQGTKLEIK (“LC”) amino acid sequence

Ab 486 971 EVQLVESGAEVKKPGESLKISCKGSG YSFTTYWIG WVRQMPGKGLEWMG IMYPG ADI-41159 Heavy chain variable region

DSQTRYSPSFQG QVTISADKSISTAYLQWSSLKASDTAMYYCA RGGYCSGGSCYRG (“HC”) amino acid sequence

LDY WGQGTLVTVSS

Ab 486 972 EIVMTQSPSSLSASVGDRVTITC RASQSISSFLN WYQQKPGKAPNLLIY AASSLLS GV ADI-41159 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSHSTPQT FGQGTKLEIK (“LC”) amino acid sequence

Ab 487 973 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYPII WVRQAPGQGLEWMG RIIPILGI ADI-41160 Heavy chain variable region

ASYAQKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYC ARNSDFYYGMDV WGQG (“HC”) amino acid sequence

TTVTVSS

Ab 487 974 QSALIQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQHHPGKAPKLMIY DVSNR ADI-41160 Light chain variable region

PS GISNRFSGSKSGNTASLTISGLQAEDEADYYCS SYTSSSLYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 488 975 EVQLVESGGGLVQPGGSLRLSCAASG FTFSTFEFN WVRQAPGKGLEWLS YISSDDT ADI-41161 Heavy chain variable region

TRYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAYYYC VRGGPYDYVWGTYRYF (“HC”) amino acid sequence

DF WGQGTLVTVSS

Ab 488 976 QSVLTQPASVSGSPGQSITISC TGTSSDIGGYNYVS WYQQHPGKAPKLMIY DVTNR ADI-41161 Light chain variable region

PL GVSNRFSGSKSGNTASLIISGLQAEDEAEYYC CSYTSSNSLV FGGGTKLTVL (“LC”) amino acid sequence

Ab 489 977 EVQLVQSGAEVKKPGSSVKVSCKASGVTG GTFSSYAIS WVRQAPGQGLEWMG GI ADI-41162 Heavy chain variable region

MPMFGTTNYAQKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYC ARDYRDFSPHL (“HC”) amino acid sequence

DYYYMDV WGKGTTVTVSS

Ab 489 978 DIRLTQSPGTLSLSPGERATLSC RASQSVSTSYLA WYQQKPGQAPRLLIY GASNRAT ADI-41162 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGRTSWT FGQGTKVDIK (“LC”) amino acid sequence

Ab 490 979 QVQLVQSGGGVVQPGRSLRLSCAASG FPFHSYAMH WVRQAPGKGLEWVA VIWY ADI-41163 Heavy chain variable region

EGSEKHYADSVQG RFTISRDNSKNMLYLQMNNLRVADTAVYYC ARRGAWGFDI W (“HC”) amino acid sequence

GQGTTVTVSS

Ab 490 980 DIVMTQTPLSLPVTPGEPASISC RSSQSVLHSTGYNSLD WYLQKPGQSPQLLIF LGSN ADI-41163 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQGLQTPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 491 981 QVQLVQSGGDLVQPGGSLRLSCAASG FTFSDYEVN WVRQAPGKGLEWLS YISSSG ADI-41164 Heavy chain variable region

RIIHYADSVRG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARAAGQWLVTYYYYG (“HC”) amino acid sequence

MDV WGQGTTVTVSS

Ab 491 982 QSVMTQSPSTLSASVGDTVTITC RASQSIINRLA WYQQKPGKPPKLLIY KSSSSES GV ADI-41164 Light chain variable region

PSKFSGSGSGTEFTLTINSLQPDDFATYYC QHYNSYLYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 492 983 EVQLVETGAEVKKPGESLKISCKGSG YSFTSYWIG WVRQMPGKGLEWMG IIYPGD ADI-41165 Heavy chain variable region

SDTRYSPSFQG QVTISADKSISTAYLQWSSLKASDTAMYYC ARRYDYIDI WGQGTM (“HC”) amino acid sequence

VTVSS

Ab 492 984 DIRVTQSPSSLSASVGDRVTITC QASQDISNYLN WYQQKPGKAPKLLIY DASNLET G ADI-41165 Light chain variable region

VPSRFSGSGSGTDFTFTISSLQPEDIATYYC QQYDNLAHIT FGPGTKVEIK (“LC”) amino acid sequence

Ab 493 985 EVQLVQSGAEVKKPGASVKVSCKTSG YTFTGDYLH WVRQAPGQGLEWMG RLNP ADI-41166 Heavy chain variable region

KSGGTVYAQRFQG RVTMTGDTSVTTAYMQLTRLRSDDTAIYYC ARGIPVSGPVSID (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 493 986 QSVLTQPASLSGSPGQSITISC TGTSSDVGGYGYVS WYQQHPGKAPKLMIY DVANR ADI-41166 Light chain variable region

PS GVSHRFSGSKSGNTASLTISGLQADDEADYYC SSYTRSNTVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 494 987 EVQLVETGGGVVQPGRSLRLSCAASG FTFSSYGMH WVRQAPGKGLEWVA VISYD ADI-41168 Heavy chain variable region

GSNKYYADSVKG RFTISRDNSKNTLYLQMNSLRTEDTAVYYC AKGGGYYYYYMDV (“HC”) amino acid sequence

WGKGTTVTVSS

Ab 494 988 QPVLTQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY GVNN ADI-41168 Light chain variable region

RPS GVSNRFSGSKSGNTASLTISGLQGEDEADYYC NSYRSGITVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 495 989 EVQLVESGAEVKKPGESLKISCEAFG YSFTSYWIG WVRQVPGRGLEWIG VIYPGDSD ADI-41169 Heavy chain variable region

IRYTPSFRG QVTISADRSISTAYLQWNNLKASDTAMYYC ARPGRDINYYHSRDYGAL (“HC”) amino acid sequence

DI WGQGTTVTVSS

Ab 495 990 DIQLTQSPDSLAVSLGERVTINC KSSQSFLYSSNNKNYLA WYQQKPGQPPKLLIY WA ADI-41169 Light chain variable region

SVRES GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC QEYYSPPMFT FGQGTKVEIK (“LC”) amino acid sequence

Ab 496 991 EVQLLESGGGLIQPGGSLRLSCAASG FTFNNYVMS WVRQAPGKGLEWVA AISSSG ADI-41170 Heavy chain variable region

VSTYYAASVKG RFTISRDNSKNMLYVQLNSLRAEDTAVYYC AKETGSYYYFDS WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 496 992 ETTLTQSPSTLSGSVGDRVTITC RASESISSWLA WYQQKPGKAPKLLIY KASNLES GV ADI-41170 Light chain variable region

PSRFSGSGSGTEFTLTISSLQPDDFATYYC QQYNSYLIT FGQGTRLEIK (“LC”) amino acid sequence

Ab 497 993 EVQLVESGPGLVKPSQTLSLTCTVSG GSISSGGDYWS WVRQRPGKGLEWIG YIYNS ADI-41171 Heavy chain variable region

GSGYYNPSLKN RVSMSMHTSRNQFSLRLSSVTAADTAFYYC ARDPFYRSGGIHYFD (“HC”) amino acid sequence

Y WGQGALVTVSS

Ab 497 994 DIVLTQTPGTLSLSPGEGATLSC RASPSVGSTSLA WYQQKPGQAPRLLIY GASSRAT ADI-41171 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQDGGLPIT FGLGTRLEIK (“LC”) amino acid sequence

Ab 498 995 EVQLLESGGGLVQPGGSLRLSCSASG FTFSVYAMH WVRLAPGKGLEYVS TISGNGG ADI-41172 Heavy chain variable region

STYYGDSVKG RFTTSRDNSKNTVYLQMSSLRAEDTAVYYCV KAPARDHYEILTLLGY (“HC”) amino acid sequence

FDY WGQGTLVTVSS

Ab 498 996 DIVMTQSPDSLAVSLGERATINC KSSQSVLYSSSNKNYLA WYQQKPGQPPKLLIY W ADI-41172 Light chain variable region

ASTRES GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC QQYYTIPPWT FGQGTKVEI (“LC”) amino acid sequence

K

Ab 499 997 QVQLVQSGAEMKKPGSSAKVSCKASG GTLSSYAIN WVRQAPGQGLEWMG GIIPIF ADI-41173 Heavy chain variable region

GTTKYAPKFQD RVTITVDESTSTAYMELSSLRSEDTAVYYC SRESSTWDVAHYFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 499 998 DIVMTQTPSAISASVGDRVTITC RASQGISNYLA WVQQKPGKVPKRLIY GASSLQS G ADI-41173 Light chain variable region

VPSRFSGSGSGTEFTLTISSLQPEDFATYYC LQHNSYPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 500 999 EVQLVESGAEVEKPGASVKVSCKASG YTFINYDII WVRQAPGQGLEWMG WISGYK ADI-41174 Heavy chain variable region

GNTNYAQKLQG RITMSTDTSTRTAYMELRSLTSDDTAVYYC ARVGGTARSTTPYYY (“HC”) amino acid sequence

GMDV WGQGTTVTVSS

Ab 500 1000 SYVLTQPPSVSVSPGQTARITC SGDAVPKQFSY WYQQKPGQAPVLVIY KDIERPS GI ADI-41174 Light chain variable region

PERFSGSSSGTTVTLTISGVQAEDEADYYC QSAHTSGTYH VFGTGTKLTVL (“LC”) amino acid sequence

Ab 501 1001 EVQLLESGGGVVQPGRSLRLSCATSG FTFSSYGMH WVRQAPGKGLEWVA VIYYEG ADI-41175 Heavy chain variable region

SNKYYGDSVKG RFTISRDNSKSTLYLQMNRLRAEDTAVYYC ARRPAGGFDY WGPG (“HC”) amino acid sequence

TLVTVSS

Ab 501 1002 EIVMTQSPLSLPVTPGEPASISC RSSQNLLNSNGYNYLD WYLQKPGQSPQLLIY LGS ADI-41175 Light chain variable region

NRAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPYT FGQGTKLEIK (“LC”) amino acid sequence

Ab 502 1003 EVQLVESGPGLVKPSETLSLTCTVSG GSIGNDYYYWG WIRQPPGKGLEWIG NISYSG ADI-41176 Heavy chain variable region

STYYNPSLKS RVTISVGTSKNQFSLKLTSVSAADTAVYHC VGRTFWRDCSSTSCYEYY (“HC”) amino acid sequence

FDY WGQGTLVTVSS

Ab 502 1004 ETTLIQSPTSLSASVGDRVTITC RASQGISNYLA WYQQKPGKVPKVLIY AASTLQS GV ADI-41176 Light chain variable region

SSRFSGSGSGTGFTLTISNLQPEDVATYYC QNYNSAPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 503 1005 QVQLVQSGAEVKKPGASVKVSCKASG YMFTGYYMH WVRQAPGQGLEWMG RIN ADI-41177 Heavy chain variable region

PNSGGTNYAQKFQG RVTMTRDTSISTGYMELSRLRSDDTAVYFC ARDFFPLVIPTLI (“HC”) amino acid sequence

VGRGLYDMDV WGQGTMVTVSS

Ab 503 1006 QPGLTQPPSASGTPGQRVTISC SGRSSNIGSNTVN WYQQLQGTAPKLLIY KNNQRP ADI-41177 Light chain variable region

S GVPDRFSGSKSGTSASLAISGLQSEDEADYYC AAWDDSLNGVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 504 1007 QVQLVESGAEVKKPGASVKVSCKASG YTFTDYYMH WVRQAPGQGLEWMG RINP ADI-41178 Heavy chain variable region

NSGGTNYAQKFQG RVTMTRDTSISTAYMELSSLRSDDTAVYYC ARDLTAGGYGST (“HC”) amino acid sequence

WYSCGDY WGQGTLVTVSS

Ab 504 1008 EIVLTQSPATLSVSPGERATLSC RASQSVSSNLA WYQQKPGQAPRLLIY GASTRAT GI ADI-41178 Light chain variable region

PARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPRWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 505 1009 QVQLVQSGAEVKKPGSSVKISCKASG GTFSSHPIS WVRQAPGQGLEWMG RIVPIF ADI-41179 Heavy chain variable region

GIANYAQKFQG RVTMIADKSTNTAYMELSNLRSEDTAVYYC ANPVYDSSGFQ WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 505 1010 QPVLTQPRSVSGSPGQSVTISC TGTSGDGGFYNYVS WYQQHPGKTPKLMIY DVDQ ADI-41179 Light chain variable region

RPS GVPDRFSGSKSGNTASLTISGLQAEDEADYYC CSYPGNPLYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 506 1011 EVQLVQSGGGLVKPGGSLRLSCAASG FTFIDYYMS WIRQAPGKGLEWVS SISGGST ADI-41180 Heavy chain variable region

YTTYADSVKG RFTISRDNGKNSLYLQMDSLRAEDTAVYYC ARLGGYSYYMDV WGK (“HC”) amino acid sequence

GTTVTVSS

Ab 506 1012 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQHLPGAAPKLLIY DNTNR ADI-41180 Light chain variable region

PS GIPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLDWV FGGGTKVTVL (“LC”) amino acid sequence

Ab 507 1013 QVQLVQSGAEVKKPGSSVKVSCKASG GSFSSYTLN WVRQAPGQGLEWMG RFVPI ADI-41181 Heavy chain variable region

VGIANYAQKFQG RVTITADKSTSTVYMELSSLRSEDTAVYYC ATAPTAYCSGDCYSLF (“HC”) amino acid sequence

DP WGQGTLVTVSS

Ab 507 1014 QSVLIQPASVSGSPGQSITISC TGISSDVGSYNLVS WYQQHPGKAPKLIIY EVNKRPS ADI-41181 Light chain variable region

GVSNRFSGSKSGNTASLTISGLQAEDEADYYC CSYAVSRTSLYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 508 1015 QVQLVQSGAEVKKPGESLKISCQGSG YSFTSYWIG WVRQMPGKDLEWMG IIYPSD ADI-41182 Heavy chain variable region

SDTRYSPSFQG QVTISVDKSINTAYLQWTSLKASDTAMYYC ARCDGAVYWYFDL W (“HC”) amino acid sequence

GRGTLVTVSS

Ab 508 1016 EIVLTQSPATLSVSPGERVTLSC RASRSVSSHLA WYQQKPGQAPRLLMY GASTRAT ADI-41182 Light chain variable region

GIPARFSGSGSGTEFTLTISSLQSEDFGVYYC QQYNNWPPALT FGGGTKLEIK (“LC”) amino acid sequence

Ab 509 1017 QVQLQESGAGLVKPSETLSLTCGVYG ESFSGHSWS WIRQPPGRGLEWIG EINQSGT ADI-41183 Heavy chain variable region

TKYNPSLRS RVTISVDRSKNEFSLKVSSVTAADTAVYFC ARYFRSFYTIGPDYYYMDV (“HC”) amino acid sequence

WGKGTTVTVSS

Ab 509 1018 EIVLTQSPSSLSASVGDRVTITC RASQNINNYL NWYQQKPGKAPRLLIY AASSLQS GV ADI-41183 Light chain variable region

PSRFTGSGSGTDFTLTIRSLQSEDFATYYC QHSYSSSLLT FGGGTKVDIK (“LC”) amino acid sequence

Ab 510 1019 EVQLLETGGGLVQPGGSLRLSCAASG FTFSSYDMN WVRQAPGKGLEWVS TISGSG ADI-41184 Heavy chain variable region

GPTYYAGSVKG RFTISRDNSKNTLYLQMNSLRADDTAVYYC AKAQLYDTSGYYLYYF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 510 1020 DIRMTQSPSSLSASVGDRVTITC RASQRITSYLN WYQQKPGKAPKLLIY AASSLQS GV ADI-41184 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYFC QQSYSTSFT FGPGTKVDIK (“LC”) amino acid sequence

Ab 511 1021 QVQLQQWGAGLLKPSETLSLTCAVYG GSFSSYYYS WIRQPPGKGLEWIG EINQSGS ADI-41185 Heavy chain variable region

TNYNPSLKS RVTISVDTSKNEFSLKLSSVTAADTAVYYC ARIVREFNTRWYDYYYMD (“HC”) amino acid sequence

V WGKGTTVTVSS

Ab 511 1022 DIRVTQSPATLSLSPGERATLSC RTSQSISSSYLA WYQQKFGQAPRLLIY GASSRAT GI ADI-41185 Light chain variable region

PDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGISPPMYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 512 1023 EVQLLESGAEVKKPGESLKISCKGSG YSFSSYWIA WVRQMPGKGLEWMG IIYPSDS ADI-41186 Heavy chain variable region

DTKYSPSFQG QVTISADKSISTAYLQWSSLKASDTAMYYC ARQAGIQRPLDY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 512 1024 EIVMTQSPATLSVSPGERATLSC RASQSVRSNLA WYQQKPGQAPRLLIY DASTRAT ADI-41186 Light chain variable region

GISARFSGSGSGTEFTLTISSLQSEDFAVYYC QQFHNWPPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 513 1025 QVQLQQWGAGLLKSSETLSLTCAVYG GSFSGYYWS WIRQSPGKGLEWIG EINHSG ADI-41188 Heavy chain variable region

SANYNPSLKN RVTISRDTSKNQFSLWLSSVTAADTAVYYC ARTSRSPEPDNYYYYM (“HC”) amino acid sequence

DV WGRGTTVTVSS

Ab 513 1026 QSVLTQPPSVSGAPGQRVSISC TGSSSDIGAGYDVH WYQQFPGTAPKLLMY ANNN ADI-41188 Light chain variable region

RPS GVPDRFSGSRSGTSASLAITGLQAEDEADYYC QSYDSNLDVVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 514 1027 QVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SMSSS ADI-41189 Heavy chain variable region

SGYIDYADSVKG RFTISRDNAKNSLYLQMNSLRVEDTAVYYC ARRNAVVVPSLMVV (“HC”) amino acid sequence

ADYYYGMDV WGQGTTVTVSS

Ab 514 1028 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-41189 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDTSLSGPGYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 515 1029 QVQLVQSGAEVKKPGASVKVSCKAFG YTFRSYDMQ WVRQAPGQRLEWMG WIN ADI-41190 Heavy chain variable region

AVNGDTKYSQKFQG RVTITRDTSATTVYMELSSLRSEDTAVYYC ARWGRFWNSRS (“HC”) amino acid sequence

LDYYAMDV WGQGTTVTVSS

Ab 515 1030 DIVMTQSPGTLSLSPGERATLSC RASQSISSSYLV WYQHKPGQAPRLLIY GASTRAT D ADI-41190 Light chain variable region

IPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPLT FGQGTRLEIK (“LC”) amino acid sequence

Ab 516 1031 QVQLVQSGAEVKRPGASVKVSCKASG YIFSHYGIS WVRQAPGQGLEWMA WISAY ADI-41191 Heavy chain variable region

NGNTNYAQKLQG RVIVTIDTSTSTAYMELRSLRSDDTAVYYC AREPPSLSAAATLD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 516 1032 EIVMTQSPLSLPVTLGQPASISC RSNQSLVYSDGNIYLS WFQQRPGQSPRRLIY KVSN ADI-41191 Light chain variable region

RDS GVPDRFSGSGSGTDFTLKISRVEAEDVAVYYC MQVTHWPHE FGQGTKLEIK (“LC”) amino acid sequence

Ab 517 1033 QVQLVQSGAEVKKPGASVKVSCRTSG YTFTDYEIN WVRQAPGQGLEWMG GISAY ADI-41192 Heavy chain variable region

NGKTDYAQNLQD RVTMTTDTSTSTAYMELRSLRSDDTAVYYC ARIFYYDRSGYYLA (“HC”) amino acid sequence

LFDS WGHGTLVTVSS

Ab 517 1034 DIQMTQSPSSLSASVGDRVTITC RASQRIASYLN WYQQKPGKAPKLLIY AASSLQS G ADI-41192 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPTLT FGGGTKMDIK (“LC”) amino acid sequence

Ab 518 1035 EVQLVESGGGLVKPGMSLRLSCAAS GFRFSDHYMN WIRQAPGKGLEWVS YISSSS ADI-41193 Heavy chain variable region

TYTDYTDSVKG RFTISRDNSKNSVYLQMNSLRAEDTAIYYC ARVAPIRHNGDYIDY W (“HC”) amino acid sequence

GQGTTVTVSS

Ab 518 1036 NFMLTQPPSASGTPGQRVTISC TGSSSNIGAGYDVH ZYQQIPGTAPKWY GNNNRP ADI-41193 Light chain variable region

SGVPDRFSGSKSGTSASLAITGLQTEDEADYYC QSYDRGLSGRV FGTGTKVTVL (“LC”) amino acid sequence

Ab 519 1037 QVQLQESGPGLVKPSQMLSLTCTVSG DSISSGDYYWS WIRHHPGKGLEWIG YISYS ADI-41194 Heavy chain variable region

GSTYNNPSLKS RVTVSVDTSKNQFFLKLTSVTAADTAVYYC ARATKPYHSYFYMDV (“HC”) amino acid sequence

WGKGTTVTVSS

Ab 519 1038 EIVLTQSPGTLSLSPGERATLSC RASQSGSRSYLA WYQQRPGQAPRLLIY GASNRAT ADI-41194 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDFAVYY CQQYGNAPT FGGGTKVDIK (“LC”) amino acid sequence

Ab 520 1039 EVQLVESGGGLVQPGGSLRLSCIVSG FPFNTYAMS WVRQAPGKGLEWVS VVSASG ADI-41196 Heavy chain variable region

GNTDYADSVKG RFTISRDNSKKTLYLQMNSLRAEDTAVYYC ARTESNTLAPSWSGR (“HC”) amino acid sequence

YVTDWYFDL WGRGTLVTVSS

Ab 520 1040 EIVMTQSPSSLSASVGDRVTITC RASQSISSFLN WYQQKPGKAPKLLIS AASSLQS GV ADI-41196 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSIPT FGQGTRLEIK (“LC”) amino acid sequence

Ab 521 1041 QVQLVQSGAEVKKPGASVKVSCKASG YTFSGYYMH WVRQAPGQGLEWVG RINP ADI-41197 Heavy chain variable region

KSGDTVYAQKFQG RVTMTRDTSISTAYMELSRLISDDTAKYYC ARQEDHYYGSGNF (“HC”) amino acid sequence

YNSFDF WGQGTLVTVSS

Ab 521 1042 ETTLTQSPSSLSASVGDRVTITC RASQSISSNLN WYQQKPGKAPKLLIY GASTLQS GV ADI-41197 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDLATYYC QQSYSNPGKT FGQGTKVDIK (“LC”) amino acid sequence

Ab 522 1043 EVQLVQSGGVVIQPGGSLRLSCAASG FSFDEYLMH WVRQLPGKGLEWVA LISWH ADI-41198 Heavy chain variable region

GDITYYADSVKG RFTISRDNSRYSLYLQMNSLRSDDTALYYC VKDGWIEGAFNHTFG (“HC”) amino acid sequence

IGYYFEN WGQGTLVTVSS

Ab 522 1044 DIVLTQTPSSLSASVGDRVTITC QASQDINNCLN WYQQKPGKAPEVLIF DASNLET G ADI-41198 Light chain variable region

VPLRFSGSGSGTHFTLTISSLQPEDIATYYC QQHENVPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 523 1045 QVQLVESGGGLVKPGGSLRLSCGASG FTFPDYYMS WIRQAPGKGLEWLS YISSSSSF ADI-41199 Heavy chain variable region

TDYADSVKG RFTISRDNAKKSLYLQMNSLRAEDTAVYYC ARVRADYVGNSRIHFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 523 1046 DIVMTQSPVTLSVSPGERATLSC RASQSLNGYLA WYQQKPGQAPRLLIY GASTRAT ADI-41199 Light chain variable region

EPGWDTSGRGSGTEFTLTISSLQSEDFAVYYC QQYNDWPFT FGQGTRLEIK (“LC”) amino acid sequence

Ab 524 1047 EVQLLESGGGLVKPGGSLRLSCAASG LTFSDHDMS WVRQAPGKGLEWVS GIGGSG ADI-41200 Heavy chain variable region

SNTYYAGSVKG RFTISRDNSKNTLYLQMDSLRVEDTAVYYC AKDPYGDYRDYYGM (“HC”) amino acid sequence

DV WGQGTTVTVSS

Ab 524 1048 DIVLTQTPFSLPVTPGEPASISC RSSQSLLKSNGYNYLD WFLQKPGQSPQLLIY LGSN ADI-41200 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQTLQALYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 525 1049 EVQLLESGGGLVQPGGSLRLSCAASG FAFDIYSMN WVRQAPGKGLEWLS YISSRGE ADI-41201 Heavy chain variable region

TIYYADSVKG RFTISRDNARNSLYLQMNGLRDEDTATYYC YYYGSGISSHGGAFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 525 1050 DIVMTQTPATLSLSPGERATLTS RASQSVSSFLA WYQQKPGQAPRLLIY DVSNRAT G ADI-41201 Light chain variable region

VPARFSGSGSGTDFTLTISSLEPEDIAVYYC QQRNTWPAIT FGQGTKVEIK (“LC”) amino acid sequence

Ab 526 1051 QVQLVESGAEVKKPGSSVKISCKASG GTFSSHPIS WVRQAPGQGLEWMG RIVPIFG ADI-41202 Heavy chain variable region

IANYAQKFQG RVTMIADKSTNTAYMELSNLRSEDTAVYYC ASPVYDSSGFQ WGQG (“HC”) amino acid sequence

TLVTVSS

Ab 526 1052 QSALIQPRSVSGSPGQSVTISC TGTSGDGGFYNYVS WYQQHPGKTPKLMIY DVDQ ADI-41202 Light chain variable region

RPS GVPDRFSGSKSGNTASLTISGLQAEDEADYYC CSYPGNPLYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 527 1053 QVQLVQSGAEVRKPGESLKISCKASG YRFTNYWIG WVRQMPGKGLEWMG VIYPG ADI-41203 Heavy chain variable region

DSDTRYSPSFQG QVTMSADKSTNTAYLQWSSLKASDTAIYYC VSLYSDYDYGALDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 527 1054 EIVMTQSPATLSVSPGERATLSC RASENVGRNLA WYQQKPGQAPRLLIY GASIRAT ADI-41203 Light chain variable region

GILARFSGSGSGTEYTLTISSLQSEDFAVYYC QQYHDWPSFT FGPGTKVDIK (“LC”) amino acid sequence

Ab 528 1055 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISAGSS ADI-41204 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARVPSYETTPYFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 528 1056 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGSGYDLH WYQQLPGTAPKLLIY VNSNRP ADI-41204 Light chain variable region

S GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 529 1057 QVQLQESGPGLVKPSGTLSLTCAVSG GSISSTNWWS WVRQPPGKGLEWIG EIYHS ADI-41205 Heavy chain variable region

GSTNYNPSLKS RVTISVDKSNNQFSLNLSSVTAADTAVYYC ARGVITYRGSWFLQYF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 529 1058 DIRVTQSPDSLAVSLGERATINC KSSQSLFYSSNNQNYLA WYQQKPGQPPKLLIY W ADI-41205 Light chain variable region

ASTRQS GVPHRFSGSGSGTDFTLTISSLQAEDVAVYYC QQYYSSPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 530 1059 EVQLLESGGGLVKPGGSLRLSCAGSG FSFSSYSMN WVRQAPEKGLEWVS SISASSSF ADI-41206 Heavy chain variable region

INYADSVKG RFIISRDNAKNSLFLQMDSLRAEDTAVYYC ARDGVHPGGYIFGGYIDS (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 530 1060 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WFRQLPGTAPKLLIY GNNNR ADI-41206 Light chain variable region

PS GVPDRFSGSKSGSSASLIITGLQAQDEATYYC QSYDSSLSGYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 531 1061 QVQLVQSGPALVKPTQTLTLTCT FSGFSLSTKGMCVS WIRQPPGKALEWLA LIDWD ADI-41207 Heavy chain variable region

DDKFYSTSLKT RLTISKDTSKNQVVLTMTNMDPVDTATYYC ARTLYFYGSGSLSDYC (“HC”) amino acid sequence

FDY WGQGTPVTVSS

Ab 531 1062 QPVLTQPRSVSGSPGQSVTISC TGTSRDVGNYNFVS WYQQHPGKAPKLIIY DVTKR ADI-41207 Light chain variable region

PS GVPDRFSGSKSGNTASLTISGLQAEDEADYYC CSYAGTYTWV FGGGTKVTVL (“LC”) amino acid sequence

Ab 532 1063 QVQLVESGGDLVKPGGSLRLSCAASG FTLSGHYMS WIRQPPGKGLEWVS SISGGST ADI-41208 Heavy chain variable region

YTNYADSVKG RFTISRDNAENSLYLQMNSLRAEDTAVYYC ARLAYSDYGPFYFDL W (“HC”) amino acid sequence

GRGTLVTVSS

Ab 532 1064 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLTGTAPKLLIF DNNNR ADI-41208 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSRLSAPYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 533 1065 QVQLQESGAGLLKPSETLSLTCAVSG ASFSGYSWS WIRQPPGKGLEWIG DIDHSGS ADI-41209 Heavy chain variable region

TNYNSSLNS RVTISVDTSKNQFSLNLTSVTAADTAIYYC ARVGGRSAY WGQGTLVTV (“HC”) amino acid sequence

SS

Ab 533 1066 DIVMTQSPLSLPVTPGEPASISC RSSQSLLHSNGFNYLD WYLQKPGQSPQLLIY LGSN ADI-41209 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 534 1067 QVQLVQSGAEVKKPGASVKVSCKASG YTFNNYGIS WVRQAPGQGLEWMG WISA ADI-41210 Heavy chain variable region

YNGDIKYAQKFQG RVTVTTDTSTSTAYMELRSLRSDDTAVYYC ARDTPVGGGTQTF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 534 1068 ETTLTQSPLSLPVTLGQPASISC RSSQSLVHSNGNTYLN WFQQRPGQSPRRLIY TVS ADI-41210 Light chain variable region

NRDS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQATHRPGT FGQGTKVEIK (“LC”) amino acid sequence

Ab 535 1069 EVQLLESGAEVKKPGASVKVSCKASG YTFTDYYIH WVRQAPGQGLEWMG RINPKN ADI-41212 Heavy chain variable region

GDAIYAQNFQG RVTMTRDTSISTAYMEVSRLTSDDTAVYYC ARDQMWLVLDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 535 1070 QSALTQPASVSGSPGQSITISC TGTSSDVGGYDYVS WYQQHPGKAPKLMIH DVTN ADI-41212 Light chain variable region

RPS GISHRFSGSKSGNTASLTISGLQAGDEADYYC SSYTRSNTKV FGTGTKVTVL (“LC”) amino acid sequence

Ab 536 1071 EVQLVESGGGLIQPGGSLRLSCAASG FTVSSNYMS WVRQAAGKGLEWVS LIYSGD ADI-41213 Heavy chain variable region

STYYADSVKG RFTISRDNSQNTLYLQMNSLRAEDTAVYYC ARDASPNVGYYGMDV (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 536 1072 DIVLTQPPSVSVSPGQTASITC SGGKLGDTYAC WYQQKPGQSPVLVIY QDSKRPS GI ADI-41213 Light chain variable region

PERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTARYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 537 1073 EVQLVESGGGLVQPGGSLRLSCAASG FTFSSYWMS WVRQAPGKGLEWVA TIKQD ADI-41214 Heavy chain variable region

GSEKYSVDSVKG RFTISRDNPKKSLYLQMNSLRAEDTAVYYC ARDYRVEYYHSSDKL (“HC”) amino acid sequence

KRYYYYGMDV WGQGTTVTVSS

Ab 537 1074 DIRVTQSPSSLSASVGDRVTITC RASQSISTYLN WYQQKPGKAPKFLIY AASSLES GVP ADI-41214 Light chain variable region

SRFSGSGSGTDFSLTISSLQPEDFATYYC QQSYSIPIT FGQGTRLEIK (“LC”) amino acid sequence

Ab 538 1075 QVQLVESGGGVVRPGGSLRLSCAASG FTFDDYGMS WVRQAPGKGLEWVS GINW ADI-41215 Heavy chain variable region

SGGSTDYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTALYYC AKEGQEWELLPW (“HC”) amino acid sequence

YFDL WGRGTLVTVSS

Ab 538 1076 QPVLTQPASVSGSPGQSITIPC TGTSSDVGIYNLVS WYQQHPGKAPKLMIY DVSKRP ADI-41215 Light chain variable region

S GVSNRFSGSKSGNTASLTISGLQAEDEADYYC CSYAGGSTYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 539 1077 EVQLVESGGGLVKPGESLRLSCAASG FRFSDHYMS WIRQAPGKGLEWIS YISSSSSYI ADI-41216 Heavy chain variable region

HYADSVTG RFTISRDNAKNSMYLQMNSLRAEDTAVYYC AREIGRSYYMDV WGKG (“HC”) amino acid sequence

TTVTVSS

Ab 539 1078 QSALIQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNNNR ADI-41216 Light chain variable region

PS GVPDRFSASKSGISASLAITGVQTEDEADYYC QSYDRSLSEFYV FGSGTKVTVL (“LC”) amino acid sequence

Ab 540 1079 EVQLVQSGGGLVKPGGSLRLSCVASG FTFSSYSMN WVRQAPGKGLEWVS SISASSS ADI-41217 Heavy chain variable region

YIDYADSVKG RFTISRDNDKKSLYLQMSSLRAEDTAVYYC AREDYDSLTGYYSPKRFD (“HC”) amino acid sequence

P WGQGTLVTVSS

Ab 540 1080 QSVLTQPPSLSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNNNR ADI-41217 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYCQ SYDRSLSVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 541 1081 QVQLVQSGAEVKKPGASVKVSCKASGY TFISDGIS WVRQAPGQGLEWMG WINPH ADI-41218 Heavy chain variable region

NENTNYAQKFQG RVTMTTDTSTSTAYLELRGLRSDDTAVYYC ARDPYHWSYLDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 541 1082 QSVVTQPPSVSGAPGQRVTITC TGSSSNIGANSDVH WYQQIPGTAPKLLIF GNSNR ADI-41218 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDRSLSGSRV FGGGTRLTVL (“LC”) amino acid sequence

Ab 542 1083 EVQLVESGGGLVQPAGSLRLSCAASG FTFSNYVMN WVRQAPGKGLEWVS YISSSG ADI-41219 Heavy chain variable region

RTIHYADSVKG RFTISRDNAKNSLYLEMNSLRAEDTAVYYC ARDPNYGGNSNRFDS (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 542 1084 DIVMTQTPSSLSASVGDRVTITC RASQTISNYLN WYQQKPGKAPKLLIF AASSLQS G ADI-41219 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSAPRVT FGPGTKVDIK (“LC”) amino acid sequence

Ab 543 1085 EVQLLESGGGLVKPGGSLRLSCAASG FTFSDYTMN WVRQAPGKGLEWVS SISITSS ADI-41221 Heavy chain variable region

HIYYADSVKG RFTISRDNAKNSLYLQINSLRAEDTAAYYC ARELGFASSSYSYYYGMD (“HC”) amino acid sequence

V WGQGTTVTVSS

Ab 543 1086 QSALTQPRSVSGSPGQSVTISC TGTSSDVGDYNSVS WYQQHPGTAPKLIIF DVTQR ADI-41221 Light chain variable region

PS GVPDRFSGSKSANTASLTISGLQPEDEADYYC CSFAGNYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 544 1087 QVTLKESGGGVVQPGRSQRLSCTASG FNFHNYAMH WVRQAPGKGLEWVA VISY ADI-41222 Heavy chain variable region

DGSNKNFADSVKG RFTISRDNSKNTLNLQMNNLRAEDTAVYYC VRDIVRGSPLFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 544 1088 QPVLTQPPSLSVAPGQTAWITC GGNNIGSKIVH WYQQKPGQAPVVVVY DDDDRP ADI-41222 Light chain variable region

S GIPERFSGSNSGNTATLTIRRVEVGDEADYYC QVWDRSSDNYV FGTGTKVSVL (“LC”) amino acid sequence

Ab 545 1089 QVQLVESGGGVVQPGRSLRISCAASG FTFSNYGMH WVRQAPGKGLEWVA VLSYD ADI-41223 Heavy chain variable region

GSNEYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKNLNDYNISWYKC (“HC”) amino acid sequence

FDL WGRGTLVTVSS

Ab 545 1090 QPVLTQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQHHPGKAPKLIIY DVNNR ADI-41223 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYIC SSYTTITTFVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 546 1091 EVQLVETGGGLVQPGRSLRLSCTASG FTFGDYAMN WVRQAPGKGLEWIG IIRTKT ADI-41224 Heavy chain variable region

YGGTTEYAASVKG RFTISRDDSKGIAYLQMNSLKTEDTGVYYC TMPVLNMDV WG (“HC”) amino acid sequence

QGTTVTVSS

Ab 546 1092 QPVLTQPHSVSESPGKTVTISC TRNIGNIASNYVQ WYQQRPGSSPTTVIY EDNQRPS ADI-41224 Light chain variable region

GVPDRFSGSIDISSNSASLTISGLKTEDEADYYC QSYDSNNPWV FGGGTQLTVL (“LC”) amino acid sequence

Ab 547 1093 EVQLVESGGGLVKPGGSLRLSCAASG FSLSDYYMT WLRQAPGKGLEWVS SIGTTST ADI-41225 Heavy chain variable region

YTNYAESVKD RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDWGFGVERGYFDL (“HC”) amino acid sequence

WGRGTLVTVSS

Ab 547 1094 DIVLTQTPSTLSASVGDRVTITC RASQSISFWLA WYQQKPGKAPKLLIY KASTLES GV ADI-41225 Light chain variable region

PSRFSGRGSGTDFTLTISSLQPDDFATYYC QQYNTYTWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 548 1095 EVQLVESGGGLVKPGGSLRLSCAASR FTFAGYYMS WIRQAPGKGLEWVS DISPSST ADI-41226 Heavy chain variable region

YTNYADSVKG RFTISRDNAGTSVSLQMDSLRADDTAVYYC ARITPYGGSHYFDS WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 548 1096 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDLH WYQQLPGTAPKLLIY GNSNR ADI-41226 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDNSLSGFYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 549 1097 RSSWCSVGAEVKKRGSSVKVSCKASG GTFGGYAVS WVRQAPGQGLEWMG GIIP ADI-41227 Heavy chain variable region

MFYTTKYAQKLQG RVTITADESTNTAYMDLSSLTSDDTAIYFC AREWHLGRTAVTG (“HC”) amino acid sequence

TGAFLDAFDI WGQGTMVTVSS

Ab 549 1098 SYELTQPPSVSEAPRQRVTISC SGSSSNIGNNAVN WYQQLPGKAPKLLIY YDDLLPS ADI-41227 Light chain variable region

GVSDRFSGSKSGTSASLAISGLQSEDEADYYC SAWDDSLNGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 550 1099 EVQLLESGPGLVKPSETLSLTCTVSG GSISSYQWN WIRQPPGKGLEWLG YVYYSGST ADI-41228 Heavy chain variable region

NYNPSLKS RVILSVDTSKNQFSLKLSSVTAADTAVYYC ARDRRDGSFVFDY WGQGT (“HC”) amino acid sequence

LVTVSS

Ab 550 1100 QSVLIQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY DVSNR ADI-41228 Light chain variable region

PS GISNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSTTLV FGTGTKVTVL (“LC”) amino acid sequence

Ab 551 1101 QVQLVQSGGGVVQPGRSLKLSCAASG FTFKSYGMH WVRQAPGKGLEWVA VISYD ADI-41229 Heavy chain variable region

EINKYYADSVKG RFTISRDYSKNTLSLQMNSLTTEDTAMYYC AKPKTTGYYYLDAFD (“HC”) amino acid sequence

F WGQGTMVTVSS

Ab 551 1102 ETTLTQSPSSLSASVGDRVTITC QASQDISNYLN WYQQKPGKAPKLLIY DASNLET G ADI-41229 Light chain variable region

VPSRFSGSGSGTDFTFTISSLQSEDIATYYC QQHDNVPPT FGQGTKVDIK (“LC”) amino acid sequence

Ab 552 1103 QVQLVQSGAEVKKPGESLKISCKASG YSFTSHYWIG WVRQMPGKGLEWMG FIFP ADI-41230 Heavy chain variable region

GDSDTRYSPSLQG QVTISADKSTNTAYLQWNSLKASDTAMYYC ARLEYLVSGFEY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 552 1104 QPGLTQPHSVSESPGKTVTISC TRSSGSIASNYVH WYQQRPGSFPTTVIY EDNQRPS ADI-41230 Light chain variable region

GVPDRFSGSIDSSSNSASLTISGLRTEDEADYYC QSYDSSNPVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 553 1105 QVQLVQSGAEVKKPGESLKISCKGSG YSFTNNWVG WVRQMPGKGLEWMG IIFPG ADI-41231 Heavy chain variable region

DSDTRYSPSFRG QVTISVDTSINTAFLQWNSLGASDTAMYYC AMTDYNYSFKS WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 553 1106 NFMLTQPHSVSESPGKTITISC TRSSGNIGNNYVQ WYQQRPGSSFTTVIY EDYQRPS ADI-41231 Light chain variable region

GVPDRFSGSIDSSSNSATLTISGLKTEDEADYYC QSYDSSNPYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 554 1107 QVQLVQSGAEVKKPGASVKVSCKASG YTFTHYGIS WVRQAPGQGLEWMA WISAY ADI-41232 Heavy chain variable region

NGNTNYAQKLQD RVIVTIDTSTSTAYMELRSLRSDDTALYYC ARDSMGGTTLFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 554 1108 DIVLTQTPLSLPVTLGQPASISC RSSQSLVYSDGNTYLN WFQQRPGQSPRRLIY KVSN ADI-41232 Light chain variable region

RDS GVPDRFTGSGSGTDFTLKISRVEAEDVGVYYC MQGTHWPPMYT FGQGTKLEI (“LC”) amino acid sequence

K

Ab 555 1109 EVQLLESGGGLVKPGGSLRLSCAASG FIFRDYYMI WIRQAPGKGLEWVS YISSSSTYT ADI-41233 Heavy chain variable region

NNADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARLFASRSDGAFDI WGQ (“HC”) amino acid sequence

GTTVTVSS

Ab 555 1110 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPETAPKLLIY DNNNR ADI-41233 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYV FGTGTTVTVL (“LC”) amino acid sequence

Ab 556 1111 QVQLVQSGGGVVQPGRSLRLSCAASG FTVSSYAIH WVRQSAGKGLEWVA VEGR F ADI-41234 Heavy chain variable region

TISRDNSKNTLYLQMNSLRAEDTAVYYC ARLSEALVEPAAHTQYKYHYGLDV WGQ (“HC”) amino acid sequence

GTTVTVSS

Ab 556 1112 EIVLTQSPLSLPVTPGEPASISC KSSQSLLDSNGYNYLD WYLQKPGQSPQLLIY LVSNR ADI-41234 Light chain variable region

AS GVPDRFSGSGSGTDFTLKISRVEAEDVGIYYC MQALQTPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 557 1113 QVQLQQWGAGLLKPSETLSLTCGVYG ESFSGHYWS WIRQPPGKGLEWMG EIHHS ADI-41235 Heavy chain variable region

GTTNYNPSLKS RVTISVDTSKNQFSLKLNSVTAADTAVYYC ARNPAEDILTGYSPPFH (“HC”) amino acid sequence

YYYMDV WGKGTTVTVSS

Ab 557 1114 QSVLIQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQIPGTAPKLLIH SNNNR ADI-41235 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 558 1115 QVQLVQSGGGLVKPGGSLRLSCTASG FTFSDYYMD WIRQAPGKGLEWVS SISSSST ADI-41236 Heavy chain variable region

YTKYADSVKG RFTISRDNAKNSLFLQMNSLRAEDTAVYYC VRNLGPYCSSTSCFVFD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 558 1116 QSVLTQPPSVSGAPGQRVSISC TGSSSNIGAGYEVH WYKQVPGTAPRLLMY DNTN ADI-41236 Light chain variable region

RPS GVPDRVSGSKSGTSASLAITGLQAEDEADYYC QSYDNSLNKSV FGGGTKVTVL (“LC”) amino acid sequence

Ab 559 1117 EVQLVESGGGLVKPGGSLRLSCAASG FTFSDYYMN WIRQAPGKGLEWVS DISPSSS ADI-41237 Heavy chain variable region

YTNYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAMYYC ARRGSCTGGVCSFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 559 1118 QPGLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVN WYQQLPGTAPKLLIY DNSNR ADI-41237 Light chain variable region

PSGVPDRFSGSKSGTSASLAITGLQAEDEADFYC QSYDSSLSGFV FGTGTKVTVL (“LC”) amino acid sequence

Ab 560 1119 EVQLLESGGGLVKPGGSLRLSCAASG FTFRDYYMS WIRQAPGKGLEWVS YISSSSSY ADI-41238 Heavy chain variable region

TEYADSVKG RFTISRDNAKKSLYLQMNSLRTEDTAVYYC ARVITQAGTGTTYYMDV (“HC”) amino acid sequence

WGKGTTVTVSS

Ab 560 1120 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGTGYDVH WYQQLPGTAPKLLIY ANNNR ADI-41238 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSLV FGGGTKLTVL (“LC”) amino acid sequence

Ab 561 1121 QITLKESGPTLVKPTQTLTLTCTFSG FSLTTTGVGVG WIRQPPGKALEWLA LIYWDD ADI-41239 Heavy chain variable region

DKRYSPSLKN RITITKDTSKKQVVLTMTNMDPADTATYYC AHISTVVTYDSSGSYYVL (“HC”) amino acid sequence

INWFDP WGQGTLVTVSS

Ab 561 1122 EIVMTQSPLSLPVTPGEPASISC RSSHSLLHSNGYNYLD WYLQKPGQSPQLLIY LGSN ADI-41239 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPLT FGQGTKVDIK (“LC”) amino acid sequence

Ab 562 1123 QVQLQQWGAGLLKPSETLSLICDVYG GSFSDYYWS WIRQSPGKGLEWIG EINHSG ADI-41240 Heavy chain variable region

STSFHPSLKS RISISIDTSNNQFSLNLSSMTAADTAVYYC ARGTLRGYFDY WGQGTLV (“HC”) amino acid sequence

TVSS

Ab 562 1124 EIVLTQSPSTLSAFVGDRVTITC RASQSISRWLA WYQQKPGKAPNLLIS EASSLES GV ADI-41240 Light chain variable region

PSRFSGSGSGTEFTLTISSLQPDDLGTYYC QQYNGYLWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 563 1125 QVQLVQSGAEVKKPGASVQVSCKASG YTFTGDYMH WVRQAPGQGLEWMG RIN ADI-41241 Heavy chain variable region

PNSGGTNYAQKFQG RVTMTRDTSISTAYMELSRLRSDDTAVYYCA RAAAEYSSSSP (“HC”) amino acid sequence

TSYYYMDV WGKGTTVTVSS

Ab 563 1126 EIQMTQSPSSLSASVGDRVTITC RASQNIYSFLN WYQQKPGKAPKLLIY AASSLQS G ADI-41241 Light chain variable region

VPSRFSGSGSATDFTLTISSLQPEDFATYYC QQSYSPPQIT FGQGTKVDIK (“LC”) amino acid sequence

Ab 564 1127 EVQLVESGGGVVQPGRSLRLSCAASG FPFSSYAMH WVRQAPGKGLEWVA VIWFE ADI-41242 Heavy chain variable region

GNEKYFADSVEG RFTISRDNSKNTLYLQMNSLRAEDTARYYC ARFYFGAFDI WGQG (“HC”) amino acid sequence

TLVTVSS

Ab 564 1128 DIVMTQSPLSLPVTPGEPASISC RSSQSLLHSNGYNSLD WYLQKPGQSPQLLIY LASN ADI-41242 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 565 1129 QVQLVQSRAEVKKPGESLKISCKGSL HSFSNNWIG WVRQMPGKGLEWMG IIFPD ADI-41243 Heavy chain variable region

DSDTRYSPSFQG QVTISADKSISTAYLQWSSLKASDTAIYYC GTVVTLIQGVAD WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 565 1130 QPVLTQPHSVSESPGKTVTISC TRSSGSIDSSYVQ WYQQRPGSSPTTVIY EDNLRPS G ADI-41243 Light chain variable region

VPDRFSGSIDSSSNSASLTISGLKTEDEAEYYC QSYDSSNPVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 566 1131 QVTLKESGGGLIQPGGSLRLSCAVSG FTVSSKYMS WVRQAPGKGLEWVS VIYGGG ADI-41244 Heavy chain variable region

STYYTDSVKG RFTISRDNSNNTLYLQMNSLRAEDTAIYYC AREARSYNYDYVGNDAF (“HC”) amino acid sequence

DI WGQGTTVTVSS

Ab 566 1132 DIVLTQTPDSLAVSLGERATINC KSSQSVLNNFNNKNYLA WYQQKPGQPPKLLIY W ADI-41244 Light chain variable region

ASTRES GVPDRFSGSGSGTDFTLTITSLQAEDVAIYYC QQYYRTPPYT FGQGTKVDIK (“LC”) amino acid sequence

Ab 567 1133 QVQLVESGGGLVKPGGSLRLSCAASG FSFSAYYMS WIRQAPGKGLEWIS NISGGSS ADI-41245 Heavy chain variable region

YANYADSVEG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREFQTYYYMDV WGK (“HC”) amino acid sequence

GTTVTVSS

Ab 567 1134 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYEVH WYQQLPGTAPKLLIY GNNNR ADI-41245 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV FGGGTKLTVL (“LC”) amino acid sequence

Ab 568 1135 EVQLLESGPGLVKPSETLSLTCIVSG GSISSYNWN WIRQPPGKGLEWIG YIYNSGSTN ADI-41246 Heavy chain variable region

YNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARYFDYGSGGFDY WGQGTLV (“HC”) amino acid sequence

TVSS

Ab 568 1136 ETTLIQSPGILSLSPGERATLSC RASQSVTSTYLA WYQQKPGQAPRLLIY GASSRAT ADI-41246 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQ QFDSSLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 569 1137 QVQLVQSGAEVKKPGASLQVSCKASG YTFTDSYFH WVRQAPGQGLEWMG RISPH ADI-41247 Heavy chain variable region

SGGTNYAQKFQG RVTMTRDTSISTAYLELSRLRSDDTAVYYC ATEGPRGPFRFDP W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 569 1138 NFMLTQPHSVSESPGKTVTISC TRSSGSIASNYVQ WYQQRPGSSPTTVIY EDNQRPS ADI-41247 Light chain variable region

GVPDRFSGSIDSSSNSASLTISGLMTEDEADYYC QSYDSSNWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 570 1139 QVQLVQSGGGVVQPGRSLRLSCAASG FTFSSYSMH WVRQAPGKGLEWMA VCW ADI-41248 Heavy chain variable region

YDGSNIYYADSVKG RFTISRDNSKNTVYLQMNSLRAEDTAVYYC ARDDRYCSGGTC (“HC”) amino acid sequence

LSAFD IWGQGTMVTVSS

Ab 570 1140 ETTLIQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGRAPKLLIY TTSSLQS GVS ADI-41248 Light chain variable region

SRFSGSGSGTDFTLTINSLQPEDFATYYC QQSYSTPNT FGQGTKVEIK (“LC”) amino acid sequence

Ab 571 1141 QVQLVQSGAEVKKPGESLKISCQVSR DTSTTYWIG WVRQMPGKGLEWMG IIFPG ADI-41249 Heavy chain variable region

DSDTRYSPSFQG QVTISADKSIMTAYLQLTSLKASDTAMYYC ATQALRGAFDI WGQ (“HC”) amino acid sequence

GTMVTVSS

Ab 571 1142 DIRLTQSPSSLSASVGDRVTITC QASQDISNYLN WYQQKPGKAPKLLIY DASYLET GV ADI-41249 Light chain variable region

PSRFSGSGSGTDFTFTISSLQPEDFATYYC QQYDDLLFT FGPGTKLEIK (“LC”) amino acid sequence

Ab 572 1143 QVQLQQWGAGLLKPSETLSLTCAVSG ESLTGYFWS WIRQPPGKGLEWIG EVSHSG ADI-41250 Heavy chain variable region

STNYNPSLKS RVIMSVDTSKTQFSLKLNSVTAADTAVYYC ARGYDYWSGTARYFDY (“HC”) amino acid sequence

WGQGILVTVSS

Ab 572 1144 QPVLTQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY DVSNR ADI-41250 Light chain variable region

PS GVSSRFSGSKSGNTASLTISGLQAEDEGDYYC SSYRSSTTSRV FGGGTKVTVL (“LC”) amino acid sequence

Ab 573 1145 EVQLVESGGGLVKPGGSLRLSCAASG FTFSDYYMT WIRQAPGKGLEWVS NISGGSS ADI-41251 Heavy chain variable region

YTNYADSVKG RFTISRDNAKNSVYLQMNSLRAEDTAVYYC ARVGCSGGVCNFFLDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 573 1146 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY DNTNR ADI-41251 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 574 1147 EVQLVQSGAEVKKPGESLKISCMGSG YNFPNYWIG WVRQMSGKGLEWMG IIYPD ADI-41252 Heavy chain variable region

DSDTTYSPSFQG QVIFSADKSISTAYLQWSSLKASDTAMYFC VRLDKTTQIDF WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 574 1148 EIVLTQSPSSLSASVGDRVTITC QASQDISNYLN WYQQKPGKAPKLLIY DVSNLET GV ADI-41252 Light chain variable region

PSRFSGSGSGTDFTFTISSLQPEDIATYYC QQHDNLPLT FGQGTRLEIK (“LC”) amino acid sequence

Ab 575 1149 EVQLVQSGPGLVKPSETLSLTCTVSG DSISSSDYSYYWG WIRQPPGKGLEWIA SLSYS ADI-41253 Heavy chain variable region

GKTYSQSSLKS RVIISVDTSKKQFSLKLSSVTAADTAVYYC AVTRCYVCTSEGDSFDM (“HC”) amino acid sequence

WGQGTMVTVSS

Ab 575 1150 DIVLTQTPGTLSLSPGERATLSC RASQSISGNYLA WYQHKPGQAPRLLIY GASTRAT G ADI-41253 Light chain variable region

IPDRFSGSGSGTDFPLTISRLEPEDFAVYYC QQYATSPYT FGQGTKVDIK (“LC”) amino acid sequence

Ab 576 1151 EVQLVESGGGLVQSGGSLRLSCAASG FTFSSYEMN WVRQAPGKGLEWVS YTTNN ADI-41254 Heavy chain variable region

GRTIYYADSVKG RFTISRDNAKNSLFLQMNGLRAEDTAVYYC ARGIQFSRVDYAMD (“HC”) amino acid sequence

V WGQGTTVTVSS

Ab 576 1152 SYELTQPPSVSGTPGQRITISC SGSSSNIASNTVN WYQHLPGTAPKLLIY SDNQRPS G ADI-41254 Light chain variable region

VPDRFSGSKSGTSASLAISGLQSEDEADYYC AIWDDSLNASYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 577 1153 EVQLVESGGGLVQPGGSLRISCAASG LTFSSYAMS WVRQAPGQGLEWVS SVSGSG ADI-41255 Heavy chain variable region

VSTYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKEDYYHFYMDV WG (“HC”) amino acid sequence

NGTTVTVSS

Ab 577 1154 ETTLTQSPATLSVSPGERATLSC RASQSVSSNLA WYQQKPGQAPRLLIY GASTRAA G ADI-41255 Light chain variable region

IPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQHDNWPSYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 578 1155 QVQLVQSGAEVKSPGSSATVSCKASG GTFGSYGIS WVRQAPGQGLEWIG AIMPM ADI-41256 Heavy chain variable region

FGTTNYAQKFQG RVTMTADESTSTVYMDVSSLRPDDTAVYYC VRDVFYDILTGYYD (“HC”) amino acid sequence

ADYYHHYMDV WGKGTTVTVSS

Ab 578 1156 DIVMTQSPLSLPVTLGQPASISC RSGQSLVHSDGNTYLN WFQQRPGQSPRRLIY KV ADI-41256 Light chain variable region

SNRGS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYFC MQGTHWPRT FGQGTKVDI (“LC”) amino acid sequence

K

Ab 579 1157 QVQLVESGAEVKKPGSSVKVSCKASE GTFSSYGIS WVRQAPGQGPEWMG EINPM ADI-41257 Heavy chain variable region

FGTAKYAQKFQG RVTITVDESTSTADMELSSLTSEDTAVYYC AREFLGQCSETNCPT (“HC”) amino acid sequence

PSRHLDY WGQGTLVTVSS

Ab 579 1158 EIVMTQSPSSLSASVGDRVTITC RASRTISSYLN WYQQKPGKAPKLLIY ATSNLQS GV ADI-41257 Light chain variable region

PSRFSGSGSGADFTLTISSLQPEDFATYYC QQTYSTPG FGPGTKVDIK (“LC”) amino acid sequence

Ab 580 1159 QVQLVQSGGGLVQRGGSLRLSCAASG FSFRSYAMS WVRQAPGKGLEWVS SISDS ADI-41258 Heavy chain variable region

GDNTFYADSVKG RFSISRDNSRDTLYLQMNSLRAEDTAVYYC ARGGYCSGGNCFPF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 580 1160 SYELMQLPSVSVSPGQTARITC SGDALPKQYGY WYQQKPGQAPVLVIY KDSERPS G ADI-41258 Light chain variable region

IPERFSGSSSGTTVTLTISGVQAEDEADYYC QSADSGGTYVM FGGGTKLTVL (“LC”) amino acid sequence

Ab 581 1161 QVQLVESGGRLVKPGGSLRLSCAASG FTFSDFYMS WIRQAPGKGLEWVS YISSSGD ADI-41259 Heavy chain variable region

D PNYADSVKG RFTISRDNSKNSLYLQMNSLRAEDTAVYYC ARDEVGWNNLDYYFG (“HC”) amino acid sequence

MDV WGQGTTVTVSS

Ab 581 1162 DIVMTQSPLSLPVTLGQPASISC RSSQSLVHSDGNTYLS WFHQRPGQSPRRLIY KVS ADI-41259 Light chain variable region

NRDS GVPNRFSGGGSGTDFTLKISRVEAEDVGFFYC MQGTHWQKT FGQGTKVEIK (“LC”) amino acid sequence

Ab 582 1163 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYGIS WVRQAPGQGLEWMG GIIPM ADI-41261 Heavy chain variable region

FGAANYAQKFQG RVTITAETSTSTAFMELSSLRSDDTAVYYC ARIRWVPNWGGTA (“HC”) amino acid sequence

TSFYNGMDV WGQGTTVTVSS

Ab 582 1164 EIVMTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLIY GASSRAT ADI-41261 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QHYGSSLFT FGPGTKVDIK (“LC”) amino acid sequence

Ab 583 1165 QVQLVQSGAEVKKPGASVKVYCKASG YTFTSHYIH WVRQAPGQGLEWMG RMNP ADI-41263 Heavy chain variable region

SGGSPMYAQKFQE RVTMTRDTSTSTAYMELRSLRSEDTAVYYC AMAKFYSFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 583 1166 QSVLTQPHSVSESPGKTVTISC TRSSGSIASYFVH WYQQRPGSAPTIVIY EDNQRPS G ADI-41263 Light chain variable region

VPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDSSNWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 584 1167 EVQLVESGGGLVKPGGSLRLSCAASG FTFSNTWMS WVRQAPGKGLEWVG HIKSK ADI-41264 Heavy chain variable region

TDGGTTDYAAPVKG RFTISRDDSKSILNLHLNSLKTEDSAVYYC AALPPISGWYYTPG (“HC”) amino acid sequence

F WGQGTLVTVSS

Ab 584 1168 SYELTQPPSMSVSPGQTARITC FGDAVPKKYVY WYQQKSGQAPVMVIY DDRRRPS ADI-41264 Light chain variable region

GIPERFSGSSSGARATLTISGAQVEDEADYYC YSTDGSGNPS FGGGTKLTVL (“LC”) amino acid sequence

Ab 585 1169 EVQLVQSGAEVKKPGESLTISCKDSG YSFTSYWIG WVRQVPGKGLEWMG IVYPGD ADI-41265 Heavy chain variable region

SRYSPSFQG HVTMSADKSINTAYLQWSTLKASDTAMYYC AKVVTYGSAIRWFES W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 585 1170 QSVLTQPPSVSAAPGQKVSISCS GSSSNIGNNFVS WYQQVPGTAPKLLII DNNKRPS ADI-41265 Light chain variable region

GIPDRFSGSKSGTSATLGITGLQTGDEADYYC GTWDSRLSAEV FGGGTKLTVL (“LC”) amino acid sequence

Ab 586 1171 QVQLQQSGPGLVKPSQTLSLTCAISG DSVSSNSAAWN WIRQSPSRGLEWLG RTYY ADI-41266 Heavy chain variable region

RSKWYNDYAVSVKS RITINPDTSKNQFSLQLNSVTPEDTAVYYC ARDLPQVDYFDG (“HC”) amino acid sequence

ASFYFFDF WGQGTLVTVSS

Ab 586 1172 QPVLTQPPSVSVAPGQTASIT CGGNIIGNKGVH WYQQKPGRAPVLVVY DDSDRPS ADI-41266 Light chain variable region

GIPERFSGSNSGNTATLTISRVEAADEADYYC QVWDTGSHPVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 587 1173 QVQLVQSGPGLVKPSGTLSLTCAVSG GSISTTHWW SWVRQPPGKGLEWIG EIYHS ADI-41267 Heavy chain variable region

GSTNYNPSLKS RVTISVDKSRSQFSLKLTSVTAADTAVYYC ARGDPLCSGGICYSGYF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 587 1174 SYVLTQPPSVSVSPGQTATITC SGDKLGDQYAC WYQQKSGQSPVLVIY RDNKRPS G ADI-41267 Light chain variable region

IPERFSGSNSGNTATLTISETQAMDEADYYC QAWGSSSVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 588 1175 EVQLVESGGGLVKPGGSLRLSCVASG FGFTSYSMN WVRQAPGKGLEWVS SISASST ADI-41268 Heavy chain variable region

YIHYADSVKG RFTISRDNARNSLYLQMISLRADDTAVYYC SRDGPTYGSGVHV WGQ (“HC”) amino acid sequence

GTMVTVSS

Ab 588 1176 QSALIQPVSVSGSPGQSITISCTG TRSDVGGYNYVS WYQQHPGKAPKLMIY EVRNR ADI-41268 Light chain variable region

PS GVSDRFSGSKSGNTASLTISGLQAEDEGDYYC SSYTSSDTLFYV FGSGTKLTVL (“LC”) amino acid sequence

Ab 589 1177 EVQLVESGGGVVQPGQSLRLSCAASG FTFSSFAMH WVRQAPGKGLEWVA VISYD ADI-41270 Heavy chain variable region

GSNKYYADSVKG RFTISRDNSKNTLSLQVNSLRAEDTAVYYC ARVSAEGSMGRFSD (“HC”) amino acid sequence

FNY WGLGTLVTVSS

Ab 589 1178 QSALTQPASVSGSPGQSITISC TGTSSDVGSYNLVS WYQQHPGKAPKLMIY EVRKR ADI-41270 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC CSYAGSDTYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 590 1179 QVQLQESGPGLVKPSQTLSLTCAISG DSVSSNNAAWN WIRQSPSRGLEWLG RTYY ADI-41271 Heavy chain variable region

RSKWYNDYAVSVKS RITINPDTSKNQLSLQLNSVTPEDTAVYYC ARAGVRQWLVRG (“HC”) amino acid sequence

MDAFDI WGQGTMVTVSS

Ab 590 1180 DIRLTQSPDSLAVSLGERATVNC KSSQSVLYSSNNKNYLA WYQQKPGQPPKLLIY W ADI-41271 Light chain variable region

ASTRES GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC QQYYNTPHT FGQGTKVEIK (“LC”) amino acid sequence

Ab 591 1181 EVQLLESGGDLVRPGGSLRLSCTASG FSFSSSEMN WVRQAPGKGLEWVA SINSGG ADI-41273 Heavy chain variable region

DDIYYADSVKG RFTISRDNAKNSLSLQMDSLRAEDTALYYC ARSRSGYSSGWSRFFG (“HC”) amino acid sequence

N WGQGTLVTVSS

Ab 591 1182 QSALTQPRSVSGSPGQSVTISC TGTISDIGAYNYVS WYQQHPGKAPKVMIY DVSKR ADI-41273 Light chain variable region

PS GVPDRFSGSKSGFTASLTISGLQAEDEADYYC CSYAGRWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 592 1183 EVQLVESGGGLVKPGGSLRLSCAASG FSFSSYAMN WVRQAPGKGLQWVS SISAGS ADI-41274 Heavy chain variable region

SYIDYADSVKG RFTISRDNAENSLFLQMNSLRVEDTAVYYC ARVGSYTHGYEFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 592 1184 QPVLTQPPSVSGAPGQRVTISC TGSNSNIGAGYDVH WYQQLPGTAPKLLIY ASTIRP ADI-41274 Light chain variable region

S GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDRNLSVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 593 1185 EVQLVESGGGLVKPGGSLRLSCAASG FMFSTYSMN WVRQAPGKGLEWVS FITGSS ADI-41275 Heavy chain variable region

SDKYYAHSVKG RFTISRDNAKRTLYLQLNSLRAEDTAVYYC ARFRGLYCDGDCSSRG (“HC”) amino acid sequence

NTYYNYYGMDV WGQGTTVTVSS

Ab 593 1186 EIVMTQSPLSLSVIPGEPASISC RSSKSLLHSNGYTYLD WYLQKPGQSPQLLIH LGSNR ADI-41275 Light chain variable region

AS GVPDRFSGSGSGTDFTLKISRVEAEDVGVFYC MQALQAPPT FGPGTKVEIK (“LC”) amino acid sequence

Ab 594 1187 EVQLVESGGGLVQPGRSLRLSCRASG FTFRNYAMS WVRQAPGKGLEWVG FIRGK ADI-41276 Heavy chain variable region

GYGGTTEYAASVKG RFTISSDDSRSIAYLQMNSLKTEDTAVYYC TRVREDGVIAVAE (“HC”) amino acid sequence

YYFDY WGQGTLVTVSS

Ab 594 1188 GIQMTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLIH GASSRAT ADI-41276 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSSPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 595 1189 QVQLQESGPGLVKPSGTLSLTCAVSG GSITGRNWWS WVRQPPGKELERIG EIYHG ADI-41277 Heavy chain variable region

GSTEYNPSLKG RVTISVDKSKNQFSLRLNSVTAADTAVYYC ARVAHYDSNGYYIGYF (“HC”) amino acid sequence

DL WGRGTLVTVSS

Ab 595 1190 EIVLTQSPPSLSASVGDRVTITC RASQSISIYLN WYQQKPGKAPKLLIF AASSLQS GVP ADI-41277 Light chain variable region

LRFSGSGSGTDFTLTISSLQPEDFATYYC HQSYSAPWT FGQGTKVDIK (“LC”) amino acid sequence

Ab 596 1191 EVQLVESGPALVKPTQTLTLTCTFSG FSLSTKRMGVS WIRQPPGKALEWLA RIDWD ADI-41278 Heavy chain variable region

DDKFYSTSLKT RLTISKDTSKNQVVLTLANMDPVDTATYFC ARTTVYASGGYYLYYLD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 596 1192 DIVMTQTPSSLSASVGDRVTLTC RASQRIASYVN WYHQKPGKAPNLLIY AASNLQS ADI-41278 Light chain variable region

GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPLT FGQGTKLEIK (“LC”) amino acid sequence

Ab 597 1193 QVQLVQSGAEVKKAGETLKISCRGPA HTFTSFWIG WVRQTPGKGLEWMG NIYPG ADI-41279 Heavy chain variable region

DTDTTYSPSFRG QVTISADKSISTAYLQWNSLKASDTAIYYC ATRVRHGYSSSGSFES (“HC”) amino acid sequence

WGQGTMVTVSS

Ab 597 1194 QSVVTQPPSVSGAPGQRITISC TGSNSNTGAGYDVH WYQQLPGAAPKLLIF ANNN ADI-41279 Light chain variable region

RPS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDNSLSAYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 598 1195 QVQLVESGPGLVKPSETLALTCTVSG GSLSTYYWS WIRQPPGKGLEWIG YIYYSGTT ADI-41280 Heavy chain variable region

YYNPSLKS RVTISEDRSKNQFSLKLTSVTAADTAVYYCA RHGPKTEFWSAQYYLEL W (“HC”) amino acid sequence

GRGTLVTVSS

Ab 598 1196 EIVLTQSPGTLSLSPGERATLSC RASQSVSSDYLA WYQQKPGQAPSLLIY GVSTRAT G ADI-41280 Light chain variable region

IPDRISGSGSGTDFTLTISRLEPEDFAVYYC HQYGTSPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 599 1197 QVQLVQSGAEVKKPGASVKVSCKASG YSFTNHGIH WVRQAPGQRLEWMG WINV ADI-41281 Heavy chain variable region

ANGFTAYSQNLQG RVTFTRDTSASTAYLELTSLRSEDTAVYHC ARDESYCSAGYCYL (“HC”) amino acid sequence

YFDY WGQGTTVTVSS

Ab 599 1198 DIQVTQSPSSLSASVGDRVTITC RASQNIITYVN WYQQKPGKAPELLIF GASSVQS G ADI-41281 Light chain variable region

VPSRFSGSGSGTDFTLTISSLRPDDFATYYC QQSYSNPRT FGGGTKVEIK (“LC”) amino acid sequence

Ab 600 1199 QVQLVQSGGGVVQPGRSLRLSCAASG FMFTIYSMH WVRQAPGKGLEWVA VISN ADI-41282 Heavy chain variable region

DGVNKYYSDSVKG RFTISRDNSKNTLYLQMNNLRAEDTAVYYC ASDIVVLVTATDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 600 1200 ETTLTQSPVTLSLSPGERATLSC RTSQSFSSPLLA WYQQKPGQAPRLLIY GASNRAT G ADI-41282 Light chain variable region

IPDRFSGSGSGTDFTLTISRLEPVDFAVYYC QQYGSSPYT FGQGTKLEIK (“LC”) amino acid sequence

Ab 601 1201 QVTLKESGPTLVKPTQTLTLTCTFSG FSLSTFGVAVG WIRQPPGKALEWLA LIYWDD ADI-41283 Heavy chain variable region

DKRYSPSLKS RLTITKDISKNQVVLTMTNMDPVDTATYYC AHRLRSLTARGVFDI WG (“HC”) amino acid sequence

QGTTVTVSS

Ab 601 1202 DIRLTQSPSSLSASVGDRVTITC RASQSINNFLN WYQQRPGKAPTLLIY SASSLQS GV ADI-41283 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYFC QQTDSFPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 602 1203 QVQLVQSGGGLVKPGGSLRLSCAASG FTFSNAWMS WVRQAPGKGLEWVG RIKSE ADI-41284 Heavy chain variable region

VDGGTADYAANVKG RLTISRDDSKNMMYLQMNSLKTEDTAVYY CTTDPGVGWIF (“HC”) amino acid sequence

GEVKLFRTDPEY WGQGTLVTVSS

Ab 602 1204 QSVLTQPPSVSAAPGQKVTISC SGSSSNIGNHYVS WYQQLPGTSPKLLIY DNNKRPS ADI-41284 Light chain variable region

GIPDRFSGSKSGTSATLGITGLQPGDEADYYC GTWDSSLSAVRV FGGGTKVTVL (“LC”) amino acid sequence

Ab 603 1205 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSYYAIS WVRQAPGQGLEWMG GIIPIL ADI-41285 Heavy chain variable region

GTVKNAQKFQG RVTITADKITSIAYMELSSLRHEDTAVYYC ARDYYDSSGYYYNGYG (“HC”) amino acid sequence

MDV WGQGTTVTVSS

Ab 603 1206 QSVLIQPPSASGTPGQRVTISC SGSSSNIGSNYVY WYQQLPGTAPKLLIY RNDQRPS ADI-41285 Light chain variable region

GVPDRFSGSKSGTSASLAISGLRSGDEADYYC AAWDDSLGGPIWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 604 1207 QVQLVQSGAEVKKPGASVKVSCKASG YTFISYGIS WVRQAPGQGPEWMG WISTH ADI-41286 Heavy chain variable region

NGNTNYAQKLQG RVTMTTDTSTSTAYMELRSLRSDDTAVYYC ARDERSIAVEVYLG (“HC”) amino acid sequence

STFDI WGQGTMVTVSS

Ab 604 1208 DIQVTQSPSSVSASVGDRVTITC RASQGISSWLA WYQQKPGKAPKLLIY AASTLQS G ADI-41286 Light chain variable region

VPSRFSGSGSGTDFTLTISRLQPEDFATYYC QQANIFGVT FGPGTKVDIK (“LC”) amino acid sequence

Ab 605 1209 EVQLVESGGGLVQPGRSLRLSCAASG FTFDDYAMH WVRQAPGKGLEWVS SISWH ADI-41287 Heavy chain variable region

SADIGYAASVEG RFTISRDNAKNSLFLQMNSLRPEDTALYYC AKEIVSTSWYSGYFQ (“HC”) amino acid sequence

D WGQGTLVTVSS

Ab 605 1210 QPVLTQPRSVSGSPGQSVTISC TGTSSDVGDYNYVS WYQQHPGKAPKLMIY DVSK ADI-41287 Light chain variable region

RPS GVPDRFSGSKSGNTASLTISGLQGEDEADYYC CSYAGRHTFV FGTATKVTVL (“LC”) amino acid sequence

Ab 606 1211 EVQLVESGGGLVQPGGSLRLSCAASG FTFSSYAMS WVRQAAGKGLEWVS AISGSG ADI-41288 Heavy chain variable region

DDTFYADSVKD RFIISRDSSKRKVYLQMNSLRVEDTAVYYC AKTDIMVTFGGVVVD (“HC”) amino acid sequence

AYYFDH WGQGTLVTVSS

Ab 606 1212 ETTLIQSPGILSLSPGERATLSC RASQFVFRSYLA WYQQRPGQPPRLLIY GASSRAT G ADI-41288 Light chain variable region

IPDRFSGRGSGTEFTLTISRLEPEDFAMYYC QHYDSSPPGT FGGGTKVEIK (“LC”) amino acid sequence

Ab 607 1213 EVQLVQSGAEVKKPGESLKISCKGSG YSFSSFWIG WVRQMPGKGLEWMG IIYPGD ADI-41289 Heavy chain variable region

SDTRYSPSFQG QVTISADQSIRTAYLQWNSLKASDTGLYYC AKGGLGDVEMATIAV (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 607 1214 QSVLIQPASVSGSPGQSITIPC TGTSSDVGSYNLVS WYQHHPGKAPKLIIS EGSKRPL ADI-41289 Light chain variable region

GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYVRSRTFNYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 608 1215 QVQLQQWGAGLLKPSETLSLTCVVYG ESFSDSGYYWT WIRQPPEKGLEWIG EINH ADI-41291 Heavy chain variable region

GGSTSYNPSLKS RVTISVDTSENQFSLKVTSVTGADTAVYYC ARLRLGCSGGSCYSRF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 608 1216 DIQLTQSPSSLSASVGDRVTITC RASQSINSYLN WYQQKPGKAPVLLIH AASSLQG G ADI-41291 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYNTRWT FGHGTKVDIK (“LC”) amino acid sequence

Ab 609 1217 EVQLLESGGGVVQPGRSLRLSCAASG FSFSSYGIH WVRQAPGKGLECVA LMSYDGS ADI-41292 Heavy chain variable region

EKYYADSVKG RFTISRDNSKNTLYLHMNSLRREDTAVYYC AKGSHLRWSHLDYYFHL (“HC”) amino acid sequence

WGRGTLVTVSS

Ab 609 1218 DIVMTQSPSTLSASVGDRVTITC RASQSLSTWLA WYQQKPGKAPKLLIS DASNLES G ADI-41292 Light chain variable region

VPSRFSGRGSGTEFTLTISGLQPDDFATYYC QQERT FGQGTKVDIK (“LC”) amino acid sequence

Ab 610 1219 QVQLQQSGPGLAKPSQTLSLTCTVSG GPISGVDYYWS WIRQPPGKGLEWIG YIYYS ADI-41293 Heavy chain variable region

GSTYYNPSLKS RVTISVDTSKKQFSLKMSSVTAADTAVYYC ARDVGATPYYYYGMD (“HC”) amino acid sequence

V WGQGTTVTVSS

Ab 610 1220 DIVLTQSPDTLSLSPGERATLSC RASQSVRSNYLA WYQHKPGQAPRLLIY GASSRVA ADI-41293 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPSVT FGGGTKVEIK (“LC”) amino acid sequence

Ab 611 1221 EVQLLESGGGLVQPGGSLRLSCAASG FTFSAYEMN WVRQAPGKGLEWVS YISSSG ADI-41294 Heavy chain variable region

SNKHYADSVKG RFTISRDNAKNSLHLHMNSLRAEDTALYYC TRPHQEEWELLPNDA (“HC”) amino acid sequence

FDL WGQGTMVTVSS

Ab 611 1222 QSALTQPPSASGSPGQSVTISC TGTSTDVGAYTYVS WYQQHPGKAPKLIIY EVYKRP ADI-41294 Light chain variable region

S GVPNRFFGSKSGNTASLTVSGLQAEDEADYYC SSYGGSNNFGL FGGGTKLIVL (“LC”) amino acid sequence

Ab 612 1223 EVQLVESGVEVKKPGESLKISCRGSG YTFYNYWIA WVRQKPGKGLEYMG TIYLDDS ADI-41296 Heavy chain variable region

ETIYSPSFQGE VTISADKSINTAYLQWNSLKASDTANYYC ARQMDFYFDV WGRGTL (“HC”) amino acid sequence

VTVSS

Ab 612 1224 SYELMQPPSVSVSPGQTARITC SGDPLPRESAY WYQQKPGQAPVVIIF NDIERPL GI ADI-41296 Light chain variable region

PERFSGSRSGTTVTLTISGAQAEDEADYYC QSADSRKTFV FGTGTKLTVL (“LC”) amino acid sequence

Ab 613 1225 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSTDAIS WVRQAPGQGLEWMG GIIPLF ADI-41297 Heavy chain variable region

GTANYAQKFQG RVTITADESTSTAYMELNSLRSVDTAVYYC GRTGAFDGEVVVRP (“HC”) amino acid sequence

HLDL WGQGTLVTVSS

Ab 613 1226 QPVLTQPASVSGSPGQSITISC TGTSSDVGGYDYVS WYQHHPGKAPKLMIY EVSNR ADI-41297 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQADDEAAYYC SSYTRSNTLL FGGGTKLTVL (“LC”) amino acid sequence

Ab 614 1227 EVQLVESGGGLVHPGRSLRLSCGASG FTFRSFAMH WVRQAPGKGLEWVA VISYD ADI-41299 Heavy chain variable region

GSDEYYADSVKG RFTISRDNSRNTLFLQMNRLRPEDTAIYYC ARAYCSTSNCPVLDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 614 1228 QSVLIQPASVSGSPGQSITISC TGTSSDVGGYSLVS WYQQHPGKAPKLIIF EGNKRPA ADI-41299 Light chain variable region

GVSDRFSGSKYGDTASLTISGLQAEDEADYYC CSYAGGHSV FGGGTKVTVL (“LC”) amino acid sequence

Ab 615 1229 QVQLVESGGGVVQPGRSLRLSCAASG FTFSSYAMQ WVRQAPGKGLEWVA VMTN ADI-41302 Heavy chain variable region

DGDDKYYADSVRG RFTISRDNSKNTLYLQMNNLRPEDTAVYYC ARDLFEWWELLG (“HC”) amino acid sequence

YCYAMDV WGQGTTVTVSS

Ab 615 1230 QSVLTQPPSASGSPGQSVTISC TGTSSDVGAYNYVS WYQQHPGKAPKLIIY EVYKRP ADI-41302 Light chain variable region

S GVPDRFFGSKSGNTASLTVSGLQAEDEADYYC SSYAGSNTLGV FGGGTKVTVL (“LC”) amino acid sequence

Ab 616 1231 QVQLVQSGGGLVRPGGSLRVSCAASG FIFNNYALT WVRQAPGKGLEWVS AISGSG ADI-41303 Heavy chain variable region

SSTYYADSVKG RFTISRENSNNRLYLQLSGLRAEDTAVYFC ARVRGLVWFEGRIDPY (“HC”) amino acid sequence

PNVFDY WGQGTLVTVSS

Ab 616 1232 DIVLTQSPGTLSLSPGERATLSC RASQSVSNDYLA WYQQKPGQAPRLLIY DASSRAI ADI-41303 Light chain variable region

GIPDRFSGSGSGTDFTLIISRLEPEDFAVYYC HHPGK FGQGTKVEIK (“LC”) amino acid sequence

Ab 617 1233 EVQLVESGPGLVKPSQTLSLTCTVSG GSIRSHDYYWS WIRQPPGKGLEWIG YSYYSG ADI-41304 Heavy chain variable region

STYYNPSLKS RVIISLDTSKNQFSLNLTSVTAADTAMYYC ARDRPHTSSWIPGWFDP (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 617 1234 SYELTQPPSASGTPGQRVTISC SGSSSNIGSNTVS WYQQFPGKAPKLLIY SNNERPS G ADI-41304 Light chain variable region

GPDRFSGSKSGTSASLAIGGLQSEDEANYYC AAWDDSLYAVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 618 1235 QVTLKESGPGLVKPSQTLSLICTVSG GSISGGGYYWS WIRQLPGKGLQWIG CIYDS ADI-41305 Heavy chain variable region

GTTYYNPSLKS LVTISIDTSKNQFSLKLSSVTAADTAVYYC ARGGSLDDFWSATWYFA (“HC”) amino acid sequence

LW GRGTLVTVSS

Ab 618 1236 EIVLTQSPGTLSLSPGERATLSC RASQSVSSNYLA WYQQKPGQAPRLLIY GASSRAT G ADI-41305 Light chain variable region

IPDRFSGSGSGTDFTLTISRLEPEDFAFYYC QQYGRSPYT FGPGTKLEIK (“LC”) amino acid sequence

Ab 619 1237 QVQLVESGPRLVKPSQTLSLICTVSG GSIYRGDYDWN WIRQPPGKGLEWIG YISYT ADI-41306 Heavy chain variable region

GNTHYNSSLKS RLSISADTSGTHFSLKLSSVTAADTAIYYC ARDVGYGGNAAHYYYYA (“HC”) amino acid sequence

MDV WGQGTTVTVSS

Ab 619 1238 ETTLTQSPATLSLSPGERATLSC RASQSVGSSLA WYQQKVGQAPRLLIY DASSRVT GI ADI-41306 Light chain variable region

PARFSGSGSGTDFTLTISSLEPGDFAVYYC QQRSNSLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 620 1239 QVQLVESGGGLVKPGGSLRLSCAASG FPLSPYALN WVRQAPGKGLEWVS SITSSSA ADI-41307 Heavy chain variable region

YIYYADSVKG RFTVSRDNPTNSLYLQMNSLRAEDTAVYYC ARTIPQHYYDNNGDYY (“HC”) amino acid sequence

NYGMDV WGQGTTVTVSS

Ab 620 1240 DIVLTQSPATLSVSPGQRITLSC RASQTVRSNLA WYQQKPGQPPRLLIY GASTRAT G ADI-41307 Light chain variable region

VPARFTGSGSGTEFTLTITSLQSDDFAVYYC HQYNDRPLT FGPGTKVEIK (“LC”) amino acid sequence

Ab 621 1241 EVQLVESGPGLVKPSQTLSLTCAISG DSVSSNSAAWN WIRQSPSRGLERMG RTYYR ADI-41308 Heavy chain variable region

SKWYDDYAVSVKS RIIINPDTSKNQFSLQLNSVTPEDTAVYYC ARGISTFGGVIYALEI (“HC”) amino acid sequence

WGQGTMVTVSS

Ab 621 1242 SYVLTQPASVSGSPGQSITISC TGLTSDVGGYNFVS WYQQHPGKAPKLIIY DVSHRPS ADI-41308 Light chain variable region

GVSNRFSGSESGNTASLTISGLQAEDEAHYYC SSYTRTSIVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 622 1243 EVQLLESGPGLVKPSQTLSLTCTVSG GSISSGDYYWS WVRQPPGKGLEWIG NIYHS ADI-41309 Heavy chain variable region

GSTYYKPSLKS RVSISLDTSKNQFSLKLSSVTAADTAIYYC ARDGGENYVWGTFRFLD (“HC”) amino acid sequence

V WGQGTTVTVSS

Ab 622 1244 DIRLTQSPGILSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLIY GVSSRAT G ADI-41309 Light chain variable region

IPDRFSGSGSGTDFTLTINRLEPEDFALYHC QQYGSSPHT FGQGTKVEIK (“LC”) amino acid sequence

Ab 623 1245 QVQLVQSGVEVKKPGESLKISCRGSG YSFYNYWIA WVRQKPGKGLEYMG TIYLDDS ADI-41310 Heavy chain variable region

DTIYSPSFQG EVTISADKSINTAYLQWNSLKASDTANYYC ARQMDFYFDV WGRGTL (“HC”) amino acid sequence

VTVSS

Ab 623 1246 SYELTQPPSVSVSPGQTARITC SGDPLPRESAY WYQQKPGQAPVVVIF NDIERPL GI ADI-41310 Light chain variable region

PGRFSGSRSGATATLTINGAQAEDEADYYC QSADSRKTFV FGAGTKLTVL (“LC”) amino acid sequence

Ab 624 1247 QVTLKQSGPALVKPTQTLTLTCTFSG FSLSTKRMGVS WIRQPPGKALEWLA RIDWD ADI-41311 Heavy chain variable region

DDKYYSTSLRT RLTISKDTSKNQVVLTMTDMDPVDTATYYC ARIQPYTSGGYYSYYF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 624 1248 DIQVTQSPSSLSASIGDRVTITC RASQTIASYLN WYQQKPGKAPKLLIY IASSLQS GVP ADI-41311 Light chain variable region

SRFSGSGSGTDFTLTISTLQPEDFATYYC QQSYGTPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 625 1249 QVQLQESGPGLVKPSGTLSLTCAVSG GSISSSNWWN WVRQPPGKGLEWIG EIYHS ADI-41312 Heavy chain variable region

GRTNYNPSLKS RVSISIDKFKSQFSLNLNSVTAADTAVYYC ARDLPGTPYDIVPGYYP (“HC”) amino acid sequence

GLRRHDAFDI WGQGTMVTVSS

Ab 625 1250 QSVLTQPPSASGTPGQRVTMSC SGSSSNIGSDTVN WYQQLPGTAPKLLIY SNNQR ADI-41312 Light chain variable region

PS GVPDRFSGSKSGTSASLAISGLQSEDEADYYC AAWDDSLNGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 626 1251 EVQLVESGAEVKKPGASVKVSCKASG YTFNNYDIS WVRQAPGQGLEWMG WISTY ADI-41313 Heavy chain variable region

NGNTNYAQKFQG RATMTTDTSTTTAYMELRSLRSDDSAIYYC ARVYCGGDCHNPF (“HC”) amino acid sequence

FLYFDL WGRGTLVTVSS

Ab 626 1252 SYVLTQPLSVSVALGQTARITC GGNNIGSKSVH WYQQKPGQAPLLVIY RDNNRPS G ADI-41313 Light chain variable region

IPERFSGSTSGNTATLTISRAQAGDEADYSC QVWDNSDWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 627 1253 QVQLVQSGAEVKKPGSSVKVSCKAFG GIFSSYAIS WVRQAPGQGLEWMG GIIPIFG ADI-41314 Heavy chain variable region

TTKYAQKFQG RVTITADKSTSTVYMEVSSLRFEESAVYFC ARAYCSGGTWYGGADY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 627 1254 QSVLTQPPSVSVSPGQTARITC SGDVLPKQYAY WYQQKPGQAPLLVMY KDTERPS ADI-41314 Light chain variable region

GIPERFSGSSSVTAVTLTISGVQAEDEADYYC QSADSTQEL FGGGTKLTVL (“LC”) amino acid sequence

Ab 628 1255 EVQLLESGPGLVKPSETLSLTCAVSG GSISNYYWS WIRQPPGKGLEWIA YISYSGTTN ADI-41315 Heavy chain variable region

YNPSLES RVTISVDTSKNQFSLKLNSVTAADTAVYYC ARHEFLVLPDV WGQGTLVTV (“HC”) amino acid sequence

SS

Ab 628 1256 ETTLIQSPGILSLSPGERATLSC RASQSVSSTFLA WYQQKPGQAPRLLIY AASSRAT G ADI-41315 Light chain variable region

IPDRFSGSGSGTDFTLIISRLEPEDFAVYYC QQYRSSPFS FGPGTKVEIK (“LC”) amino acid sequence

Ab 629 1257 QVQLVQSGGGVVQPGRSLRLSCAASG FTFNNYGMH WVRQAPGKGLEWVA VLSF ADI-41316 Heavy chain variable region

DGINKYYADSARG RFTISRDNSKNTLYLQMNSLRAEDTALYYC AKDRQEYSSGWTH (“HC”) amino acid sequence

DACDI WGQGTMVTVSS

Ab 629 1258 EIVMTQSPATLSVSPGERATLSC RASQNVNNNLA WYQQNPGQAPRLLIF GASTRA ADI-41316 Light chain variable region

T GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPRT FGQGTKLEIK (“LC”) amino acid sequence

Ab 630 1259 EVQLVESGGGLVQPGGSLRLSCEASR FKFSTFWMA WVRQAPGKGLEWVA NIKQD ADI-41317 Heavy chain variable region

GSETYYLDSVKG RFTISRDNAKNSLFLQMKSLRAEDTAVYYC AGLWWGDLENWFD (“HC”) amino acid sequence

P WGQGTLVTVSS

Ab 630 1260 QSVLTQPPSVSGAPGQRVTISC TGSSSNLGTGFDVH WYRQLPGTAPQLLIY GSTNR ADI-41317 Light chain variable region

PS GVPDRFSGSKYGTSASLAITGLQAEDEADYYC QSYDSNLRAYV FGTVTKVTVL (“LC”) amino acid sequence

Ab 631 1261 EVQLLESGAEVKKPGSSVRVSCKAFG GTFSSYAFS WVRQAPGQGLEWMG GITPM ADI-41318 Heavy chain variable region

FGTENYAPNFQG RVTITADKLTTTVYMELSRLRSEDSAVYYC AREGGRLGTTMGAF (“HC”) amino acid sequence

DM WGQGTMVTVSS

Ab 631 1262 DIRLTQSPSSLSASVGDRVTITC RASHGISSALA WYQQRPGRVPQVLIF HASTLES GV ADI-41318 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQFNSYPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 632 1263 QVQLQESGPGLVKPSQTLSLTCTVSG GSISSGDYYWS WIRQPPGKGLEWIG YIFYSG ADI-41319 Heavy chain variable region

TTYYNPSLKS RVTISLDTSQNQFSLKLSSVTAADTAVYYC ARDGDEVDYVWGTRRYL (“HC”) amino acid sequence

DS WGRGTLVTVSS

Ab 632 1264 EIVLTQSPGTLSLSPGERATLSC RASQSVSSRYLA WYQQKPGQAPRLLIH GASSRAT ADI-41319 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC LQYGSLPKT FGQGTKVEIK (“LC”) amino acid sequence

Ab 633 1265 QVQLVQSGVEVKKPGESLKISCRGFG YSAYNYWIA WVRQKPGKGLEYMG TIYLDD ADI-41320 Heavy chain variable region

SDTIYSPSFQG EVTISADRSINTAYLQWNSLKASDTANYYC ARQMDFYFDV WGRGT (“HC”) amino acid sequence

LVTVSS

Ab 633 1266 QSVLTQPPSVSVSPGQTARITC SGDPLPRESAY WYQQKPGQAPVVVIF NDIERPL GI ADI-41320 Light chain variable region

PARFSGSRSGTTVTLTISGAQAEDEADYYC QSADSRKTFV FGPGTKLTVL (“LC”) amino acid sequence

Ab 634 1267 QVQLVQSGAEVKKPGSSVRVSCKASG GSFSSYATS WVRQAPGQGLEWMG GIIPM ADI-41322 Heavy chain variable region

YDAVNYAQKFQG RVTITADESTTTAYMELSSLRSEDTAVYYC ARSSGYTGINFFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 634 1268 DIQMTQSPSSVSASVGDRVTITC RASQDISSWLA WYQQKPGKAPKLLIY TASSLQS G ADI-41322 Light chain variable region

VPSRFSGSGSGTDFTLTISRLQPEDFATYYC QQANSFPRVT FGGGTKVEIK (“LC”) amino acid sequence

Ab 635 1269 EVQLLESGGGVVRPGGSLRLSCAASG FTFDDYAMG WVRQAPGKGLEWVS GITW ADI-41323 Heavy chain variable region

NAGSTAYAGSVKG RFTISRDNAKNSLFLQMNSLRAEDTAFYLC ARHVDSSGPVARH (“HC”) amino acid sequence

FDY WGQGTLVTVSS

Ab 635 1270 NFMLTQPHSVSESPGKTVTISC TRSSGSIARNYVQ WYQQRPGSAPTIVIY EDNQRPS ADI-41323 Light chain variable region

GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDPSNVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 636 1271 EVQLVESGGGLVQPGGSLRLSCAASG FTVSNNYMR WVRQAPGKGLEWVS VIYSS ADI-41324 Heavy chain variable region

GSTDYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARERTLFYYDSSGFFD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 636 1272 ETTLTQSPGTLSLSPGERATLSC RASQSVDSSYLA WYQQKPGQAPRLLIY GASNRAT ADI-41324 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGRSLT FGGGTKLEIK (“LC”) amino acid sequence

Ab 637 1273 QVQLVQSGAEVKTPGSSVKVSCKASG GTFRSYPIT WVRQAPGQGLEWMG TVIPVF ADI-41340 Heavy chain variable region

DTVNYAPKFQG RVSITADESTNTAYMELSSLRSDDSAVYYC ARDLGWLRPMTTVTS (“HC”) amino acid sequence

PHFDY WGQGTLVTVSS

Ab 637 1274 QSVLTQPASVSGSPGQSITISC TGTSSDVGGYDFVS WYQQHPGKAPKLMIS EVTDR ADI-41340 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC TSYTSSRTYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 638 1275 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYATH WVRQAPGQGLEWMG GIIPIF ADI-41341 Heavy chain variable region

GRATYAQKFQG RVTISADESTSTAYMELSSLRSEDTAVYYC ARGRDDRSGDHIAFLY (“HC”) amino acid sequence

HYGMDV WGQGSTVTVSS

Ab 638 1276 QSVLTQPPSVSAAPGQKVSISC SGSSSNIGINHAS WYQHLPGTAPKLLIY DNNKRPS ADI-41341 Light chain variable region

GIPDRFSGSKSGTSATLGISGLQTGDEAAYYC GTWDTGLSAVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 639 1277 QVQLVQSGAEVKKPGSSVKVSCKASG GTLTSYGVS WVRQAPGQGLEWMG GIIPIF ADI-41342 Heavy chain variable region

GTVDYAQKFQG RVTITADEPTSTAYMELSSLTSDDTAVYYC ARDPWVSGPVEFYYY (“HC”) amino acid sequence

FDV WGRGTLVTVSS

Ab 639 1278 DIVLTESPATLSLSPGERATLSC RASQSINNRYLA WYQQKPGQAPRLLIF GASSRAT G ADI-41342 Light chain variable region

IPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSTPPT FGQGTKVEIK (“LC”) amino acid sequence

Ab 640 1279 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYYMN WVRQAPGKGLEWVS SISGGS ADI-41343 Heavy chain variable region

SYISYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARVDTPMVRGYYFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 640 1280 QSVLTQPPSVSGAPGRRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIF ANSNRP ADI-41343 Light chain variable region

S GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV FGGGTKVTVL (“LC”) amino acid sequence

Ab 641 1281 EVQLVESGGGLVKPGGSLRLSCAASG SSFSSYYMN WVRQAPGKGLEWVS SISSSST ADI-41344 Heavy chain variable region

YIDYADSVKG RFTISRDNAKNSLFLQMNSLRAEDTAVYYC ARVSSPMIRGYYLDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 641 1282 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLVIH GNSN ADI-41344 Light chain variable region

RPS GVPDRFSGSKSGTSASLAITGLQGEDEADYYC QSYDSSLSGSV FGGGTKLTVL (“LC”) amino acid sequence

Ab 642 1283 EVQLVQSGAEVRKPGESLKISCKGSG YNFASYWIA WVRQMPGKGLEWMG IIFPGD ADI-41345 Heavy chain variable region

SDTRYSPSFQG QVTISVDKSISTAYLQWSSLKASDTAIYYC ATSKYTFGYLD WGQGTL (“HC”) amino acid sequence

VTVSS

Ab 642 1284 NFMLTQPHSVSESPGKTVTISC TRSSGSIASNYVQ WYQQRPGSAPTTVIY EDNQRP ADI-41345 Light chain variable region

SGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDTSNQV FGTGTKVTVL (“LC”) amino acid sequence

Ab 643 1285 QVQLVQSGPEVKKPGESLKISCTLSA SGLTTYWIG WVRQMPAKGLEWMG IIFPGD ADI-41346 Heavy chain variable region

SDTRYSPSFQG QVTISADKSTNTAYLQWSGLKASDTAIYYC ATLQTPVTGLDQ WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 643 1286 NFMLTQPHSVSESPGKTVTISC TRSSGNIARSYVQ WYQQRPGSAPTTVIH EDDQRP ADI-41346 Light chain variable region

S GVPDRFSGSIDTSSNSASLTISGLKTEDEADYYC QSYDPSNYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 644 1287 EVQLVESGPGLVKPSGTLSLTCAVSG GSVSSDNWWS WVRQPPGKGIEWIG EIYPS ADI-41347 Heavy chain variable region

GGTNYNPSLNS RVTISVDKSKNQFSLKLNSVTAADTAIYYC ARAPFDSSGYHSNSV W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 644 1288 ETTLTQSPLSLPVTPGEPASISC RSSQSLLHSNGHNYLD WYVQKPGQSPQLLIY LSSN ADI-41347 Light chain variable region

RAS GVPDRFSGSGSGTDFTLRISRVEAEDVGVYYC MQPLQTPQT FGQGTKVEIK (“LC”) amino acid sequence

Ab 645 1289 QVQLQESGPGLVKPSQTLSLTCAVSG GSISSGGYYWS WIRQHPGKGLEWIG YIYYS ADI-41348 Heavy chain variable region

GSTYYNPSLKS PVTISVDTSKNQFSLKLTSVTAADTAVYYC ARGDYYFDGSGRTTAAF (“HC”) amino acid sequence

DI WGQGTMVTVSS

Ab 645 1290 DIQVTQSPSSLSASVGDRVTITC RASQSISTFLN WYQQKPGRAPKLLIY DASNLQS GV ADI-41348 Light chain variable region

PSRVSGSGSGTDFTLTISSLHPEDFATYYC QQSYTTPYT FGQGTKVDIK (“LC”) amino acid sequence

Ab 646 1291 EVQLLESGGGLVQPGRSLRLSCTGSG FTFGDYAMN WVRQAPGKGLEWVG LIRSKD ADI-41349 Heavy chain variable region

YGGTTEFAASLKG RLTISRDDSKSIAYLQMHSLKTEDSAVYYC TRAHLTDYTDINGYQ (“HC”) amino acid sequence

YYFDY WGQGSPVTVSS

Ab 646 1292 DIQMTQSPSSLSASVGDRVTITC QASQDISNFLN WYQQRPGKAPKLLIH DASNLET ADI-41349 Light chain variable region

GVPSRFSGSGSRTEFTFTISSLQPEDIGTYYC QHYDNFPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 647 1293 EVQLVESGAGLVQPGGSLRLSCAASG FTFSTYAVS WVRQAPGKGLEWVS AISGSG ADI-41350 Heavy chain variable region

ASTYFADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKARLELRPYYYGMD (“HC”) amino acid sequence

V WGQGTTVTVSS

Ab 647 1294 QPVLTQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQHPGKAPKLIIY EVSNRP ADI-41350 Light chain variable region

S GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSSTLSTTYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 648 1295 QVQLVQSGGGLVQPGGSLRLSCSASG FTFSSKSMH WVRQAPGKGLEYVS AIRSDG ADI-41351 Heavy chain variable region

VSTYYGDSVKG RFTVSRDNAKNTVYLRMSSLRREDTAVYYC VKGPYGDFQYNWFD (“HC”) amino acid sequence

T WGQGTLVTVSS

Ab 648 1296 ETTLIQSPATLSVSPGERATLSC RASQSVSSNLA WYQQKPGQAPRLLIY GASIRAT GI ADI-41351 Light chain variable region

PARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYDNWPPGDT FGQGTKVEIK (“LC”) amino acid sequence

Ab 649 1297 EVQLVESGGGLVQPGGSLRLSCAASG FTFSSYRMN WVRQAPGKGLEWVS YIDISSS ADI-41352 Heavy chain variable region

TIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDQLVWEPLIRNHYYY (“HC”) amino acid sequence

AMDV WGQGTTVTVSS

Ab 649 1298 EIVMTQSPDSLAVSLGERATINC KSSQSVLYSSNNKNYLA WYQQKPGQPPKLLIY W ADI-41352 Light chain variable region

ASTRES GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC QQYYSSPPT FGQGTKVEIK (“LC”) amino acid sequence

Ab 650 1299 EVQLVESGVEVKKPGESLKISCRGSG YSFHNYWIA WVRQKPGKGLEYMG TIYVDDS ADI-41353 Heavy chain variable region

DTIYSPSFQG EVTISADKSINTAYLQWNSLKASDTANYYC ARQMDFYFDV WGRGTL (“HC”) amino acid sequence

VTVSS

Ab 650 1300 SYELTQPPSVSVSPGQTARITC SGDPLPRESAY WYQQKPGQAPVVVIF NDIERPL GI ADI-41353 Light chain variable region

PERFSGSRSGTTVTLTISGAQAEDEADYYC QSADSRKTFV FGSGTKLTVL (“LC”) amino acid sequence

Ab 651 1301 EVQLLESGGGLVQPGGSLRLSCAASG FTFSSYAMS WVRQAPGKGLEWVS GISGSG ADI-41354 Heavy chain variable region

GTTYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKDSPVNINCGGDCD (“HC”) amino acid sequence

VAY WGQGTLVTVSS

Ab 651 1302 EIVMTQSPSSLSASVGDTVTITC QASQDISYSLN WYQQKPGKAPNLLIF DASHLQT G ADI-41354 Light chain variable region

VPSRFSGGGDGKHFSFTISSLQPEDVATYYC QQYDSLMYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 652 1303 EVQLVESGGGLVKPGGSLRLSCTASG FTFSDYYMN WIRQAPGKGLEWVS YISGDG ADI-41355 Heavy chain variable region

NTIYYTDSVKG RFTISRDNAKNSLFLQMNSLRGEDSAVYYCAGPVRGYTYGIFDYW (“HC”) amino acid sequence

GQGALVTVSS

Ab 652 1304 YYVLTQPPSVSVAPGQAARITC GGNNIGSRSVN WYQQKPGQAPVVVIY GDSVRPS ADI-41355 Light chain variable region

GIPERFSGSNSGNTATLTFSRVEAGDEADYYC QVWETNSDHPVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 653 1305 QVQLVQSGAEVKKPGASVKVSCKASG YTFTNYDIN WVRQATGQGLEWMG WMN ADI-41356 Heavy chain variable region

RNNGNTGYARKFQG RVTMTRNTSISTAYMELSSLRSEDTAVYYC ARGGDFYAMDV (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 653 1306 SYELTQPPSVSVSPGQTASITC SGDKLGDKYAS WYQQKPGQSPVLVIY QDTKRPS G ADI-41356 Light chain variable region

VPERFSGSNSGNTATLTISGTQAVDEADYYC QVWDGSIA FGGGTKVTVL (“LC”) amino acid sequence

Ab 654 1307 EVQLVESGGGLVQPGGSLRLSCAASG FTFSTYGMN WVRQAPGKGLEWVS YIGGS ADI-41357 Heavy chain variable region

GRIIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDQHIVLVTGSTPD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 654 1308 EIVLTQSPSSLSASVGDRVTITC RASHAISNYLA WFQQKPGKAPKSLIY AASTLQS GV ADI-41357 Light chain variable region

PSKFSGSGSGTDFTLTISSLQPEDFATYYC QQYSSYPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 655 1309 EVQLVESGGGLVKPGGSLRLSCEASG FTLTSYSM NWVRQAPGKGLEWVS SISSSST ADI-41358 Heavy chain variable region

YIHYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDKVMVTKYNGMDV (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 655 1310 QSVLTQPPAVSGAPGQRVTISC TGSSSNIGAGHDVH WYQQLPGTAPKLLIY GNSNR ADI-41358 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAGDEADYYC QSYDSSLSGSL FGGGTKLTVL (“LC”) amino acid sequence

Ab 656 1311 EVQLVESGGGLVKPGGSLRLSCAASG FTISGYSMD WVRQAPGKGLEWVS SISSSSS ADI-41359 Heavy chain variable region

YIHYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ATNPREGGAFDI WGQ (“HC”) amino acid sequence

GTTVTVSS

Ab 656 1312 QSVLTQPPSMSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY NNSNR ADI-41359 Light chain variable region

PSGVPDRFSASKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYV FGTGTRVTVP (“LC”) amino acid sequence

Ab 657 1313 EVQLVESGGGLVQPGGSLRLSCAASG LTFSRYSMN WVRQAPGKGLEWVS YISSTG ADI-41360 Heavy chain variable region

RRIQYADSVKG RFTISRDDGKNSLYLQMNSLRAEDTAVYYC ARDPLNYHDNTAYW (“HC”) amino acid sequence

SY WGQGTLVTVSS

Ab 657 1314 NFMLTQPHSVSESPGKTVTISC TRSSGSIASNYVQ WYQQRPGSAPTTVIY EDNQRP ADI-41360 Light chain variable region

SGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDSSNPLV FGGGTKLTVL (“LC”) amino acid sequence

Ab 658 1315 QVQLQESGGGVVQPGRSLRLSCAASG FAFSDYAMD WVRQAPGKGLEWVA VISFD ADI-41361 Heavy chain variable region

GSNKFYADSVKG RFTISRDNSENTLFLQMNSLRAEDTAVYYC VRDFVPCSGATCYLP (“HC”) amino acid sequence

PVY WGRGTLVTVSS

Ab 658 1316 EIVLTQSPATLSVSPGERATLSC RASQSVSSDLA WYQQKPGQAPRLLIY GASTRAT GI ADI-41361 Light chain variable region

PARFSGSGSGTEFTLTISRLQSEDFAVYFC QQYNNWPSWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 659 1317 EVQLVESGGGLVQPGGSLRLSCAASG FTFSDHWMN WVRQTPGKGLEWVA NIKP ADI-41362 Heavy chain variable region

DGRETYYVDSVKG RFTISRDNSKKSVYLQMNSLRAEDTAVYYC VRDGHIVVVTAVP (“HC”) amino acid sequence

PGFFDL WGRGTLVTVSS

Ab 659 1318 DIQVTQSPSSLSASVGDRVTITC QASQDLTKYLN WYQQKPGKAPKLLIY DISNLET G ADI-41362 Light chain variable region

VPSRFSGSGFGTEFTLTISSLQPEDVATYYC QQYQNLPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 660 1319 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYAIT WVRQAPGQGLEWMG GIIPLF ADI-41363 Heavy chain variable region

GTAKYAQQFQG RVTITADESTSTAYMELSSLRSEDTAVYYC ARDGEVCTNGFCWFL (“HC”) amino acid sequence

D WGLGTLVTVSS

Ab 660 1320 DIRVTQSPSSLSASVGDRVTITC QASQDISNYLN WYQQKPGKAPKLLIY DASKLET G ADI-41363 Light chain variable region

VPSRFSGSGSGTDFTFTISSLQPEDIATYYC QNYGNFPH FGGGTKLEIK (“LC”) amino acid sequence

Ab 661 1321 EVQLLESGAEVKKPGASVKVSCKASG YTFTDHSIH WVRQAPGRGLEWMG WFNPH ADI-41364 Heavy chain variable region

TGVTDYAQKFQG WVTMTSDTSISTAYMELSSLKSDDTAIYFC ARDQWETDGAYFL (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 661 1322 QSALTQPASVSGSPGQSITISC TGTSSDVGNFKLVS WYQQHPGKAPKLMIY EGNKR ADI-41364 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC CSSAVSSTF FGTGTKLTVL (“LC”) amino acid sequence

Ab 662 1323 EVQLVESGGGLVKPGGSLRLSCATSG FTFSDYYMT WIRQAPGKGLEWVS YISSSGG ADI-41365 Heavy chain variable region

YTNYADSVRGR FTISRDNAKRSLYLQMNSLRAEDTAVYYC ARVEFSSGDVPSLFDS (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 662 1324 QSVLTQPPSVSGAPGQRVTISC TGSSSNLGAGYHVH WYQQFPGTAPKPLIY GNTN ADI-41365 Light chain variable region

RPS GVPDRFSGSKSGTSASLAITGVQAEDEADYYC QSYDYSLSGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 663 1325 QVQLVQSGAEVKKPGESLKISCKASG YSSTTYWIG WVRQISGKGLEWMG IIYPGDS ADI-41366 Heavy chain variable region

DTRYSPSFQG QVTISADRSTKTAYLQWSSLKASDTAMYYC GTSGFGVATPFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 663 1326 NFMLTQPHSVSESPGKTVTISC TRTSGSIAGNYVH WYQQRPGSAPTTVIY EDNQRP ADI-41366 Light chain variable region

S GVPDRFSGSIDRSSNSASLTISGLKTEDEADYYC QSYASGIHGV FGGGTKVTVL (“LC”) amino acid sequence

Ab 664 1327 QVQLVQSGAAVKRPGASVKVSCKASG YTFSTNALH WVRQAPGQSLEWMG WINT ADI-41367 Heavy chain variable region

DNGIPKYSERFHG RVTFTRDTSASTVYMDLSGLRSGDTAVYYC ARDGSSGHWLGLS (“HC”) amino acid sequence

VLDN WGQGTLVTVSS

Ab 664 1328 QSALIQPASVSGSPGQSITISC TGTSDDVGAYNYVS WYQQYPNKAPKLVIY EVSHRP ADI-41367 Light chain variable region

S GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTRSATPYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 665 1329 EVQLVESGGGVVQPGRSLRLSCAASG FIFRNYGMH WVRQAPGKGLEWVA GTSFE ADI-41368 Heavy chain variable region

GRNKDYGHSVKG RFTISRDNSKDTLYLQMNSLRPEDTAVYSC AKGSSLQWSHLDW (“HC”) amino acid sequence

YFDL WGRGTLVTVSS

Ab 665 1330 DIVMTQSPSTLSASVGDRVTITC RASQSFSSWLA WYQQKPGKAPNLLIY DASTLES G ADI-41368 Light chain variable region

VPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQERT FGQGTKVEIK (“LC”) amino acid sequence

Ab 666 1331 EVQLVQSGGGVVQPGRSLRLSCAASG FTFSSYGMH WVRQAPGKGLEWVA VISHD ADI-41369 Heavy chain variable region

GNNKYYGDSVKG RFTISRDNSKNTLHLQMNSLRGDDTAVYYC GKDPLKGDCSGGS (“HC”) amino acid sequence

CYQRIDY WGQGTLVTVSS

Ab 666 1332 NFMLTQPHSVSESPGKTVTISC TGSSGRIASNYVQ WYQQRPGSAPATVIY DDNQRP ADI-41369 Light chain variable region

S GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDRSNHVI FGGGTKLTVL (“LC”) amino acid sequence

Ab 667 1333 EVQLVESGGGLVKPGGSLRLSCAASG FTFSGFSMN WVRQAPGKGLEWVS SISSTSR ADI-41370 Heavy chain variable region

YIYYADSVQG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDPGGSASFVPYYYG (“HC”) amino acid sequence

MDV WGQGATVTVSS

Ab 667 1334 SYELIQPPSVSVSPGQTARITC SGDALPNQYVY WYQKKPGQAPVLVIY KDTEGPL GI ADI-41370 Light chain variable region

PERFSGSSSGTTVTLTISGVQAEDEADYYC QSADSSGTYPYVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 668 1335 QVQLQESGPRLVKPSQTLSLTCTVSG GSITTGEHYWS WIRQSPGRGLEWIG YISYSG ADI-41371 Heavy chain variable region

STYYNPSLKS RVTISVDTSKTRISLNLRSVTAADSAVYYC ARDQEDSDYIWGSSRVFDI (“HC”) amino acid sequence

WGQGTMVTVSS

Ab 668 1336 ETTLTQSPGTLSLSPGERATLSC RASQNVGNNYLA WYQQKPGQAPRVLIQ DASTRA ADI-41371 Light chain variable region

T GIPDRFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSAPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 669 1337 QVQLVQSGAEVKKPGSSVKVSCKASG GISSSYAIS WVRQAPGQGLEWMG GIIPIFG ADI-41372 Heavy chain variable region

TTNYAQKFQG RVTITADKSTSTVYMELSSLRSEDSAVYFC ARAYCSGGTCYGGADY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 669 1338 SYELTQPPSVSVSPGQTARITC SGDVLPKQYAY WYQQKLGQAPLLVMY KDTERPS G ADI-41372 Light chain variable region

IPERFSGSSSVTAVTLTISGVQAEDEADYYC QSADSTQEL FGGGTKLTVL (“LC”) amino acid sequence

Ab 670 1339 QVTLKESGGGLVKPGGSLRLSCAASG FTFSDYFMT WIRQAPGKGLEWVS YISSNSG ADI-41373 Heavy chain variable region

YTKYAEDVKG RFSISRDNAKKTLFLQLNSLSAEDTAVYYC ARVEFSSGDVPSLFDL W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 670 1340 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYHVH WYQQLPGTAPKVLIH GNNN ADI-41373 Light chain variable region

RPS GVPDRFSGSRSGTSASLAITGLQAEDEADYYC QSYDFSLSGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 671 1341 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSNHAID WVRQAPGQGLEWMG RIIPM ADI-41374 Heavy chain variable region

VGLATYTRKFQG RVTISVDKSTSTAYMELSSLISDDTAVYYC ARRTPEMAWGY WG (“HC”) amino acid sequence

QGTTVTVSS

Ab 671 1342 DIVMTQTPSSLSASVGDRVTITC QASQDIRYYVN WYQQKPGKAPKLLIY DASTLET G ADI-41374 Light chain variable region

VPSRFSGRGSGTDFTLIISSLQPEDIATYYC QQYGDLPT FGQGTRLEIK (“LC”) amino acid sequence

Ab 672 1343 QVQLVQSGGGVVQPGRSLRLSCATSG FTFSDYAIH WVRQAPGKGLEWVA VISYDG ADI-41375 Heavy chain variable region

SHKYYGDSVKG RFTISRDNSKNTLYLQMNSLRPEDTAVYYC ARSRSGSYYSSAIDN W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 672 1344 DIQMTQSPSSLSASVGDRVTIAC RASQGISSALA WYRQRPGKAPELLIY DASTLES G ADI-41375 Light chain variable region

VPSRFSGYGAGTDFTLTISSLQPEDFATYYC QQFNSYPSIT FGQGTKVEIK (“LC”) amino acid sequence

Ab 673 1345 QVQLQESGGGVVQPGRSLRLSCAASG FTFSSYAM HWVRQAPGKGLEWVA VISFD ADI-41376 Heavy chain variable region

GTANKYYADSVKG RFAISRDNSKNTLYLQMNSLRAEDTAVYYC AKDDAIYSGGWV (“HC”) amino acid sequence

GDAFDL WGQGTMVTVSS

Ab 673 1346 EIVLTQSPATLSVSPGERATLSC RASQGVNSNLA WYQQKPGQAPRLLMY GASTRAT ADI-41376 Light chain variable region

GIPARFSGSGSETEFTLTISSLQSEDFAVYYC QQYNNWPRT FGQGTKVDIK (“LC”) amino acid sequence

Ab 674 1347 QVQLQQSGPGLVKPSQTLSLTCAISG DSVSSDSATWN WIRQSPSRGLEWLG RAYY ADI-41377 Heavy chain variable region

RSKWYYDYAPSVKS RLTINPDTSKNQFSLQLTSVTPQDTAVYFC ARDLPPLEYFDGS (“HC”) amino acid sequence

GYYFLDH WGQGTLVTVSS

Ab 674 1348 SYELTQPPSVSVAPGQTARLSC GGHNIGSKSVQ WYQQKPDQAPVLVVY DDHDRPS ADI-41377 Light chain variable region

GIPDRFSGSNSGDMATLTISRVEAGDEADYYC QVCESGRDPMV FGGGTKVTVL (“LC”) amino acid sequence

Ab 675 1349 EVQLVESGPGLVKPSGTLSLTCAVSG DSISSSNWWS WVRQPPGKGLEWIG EVSHS ADI-41378 Heavy chain variable region

GNTDYNPSLKS RVTISVDKSKNQFSLKLSSVTAADTAVYYC ARPSPCSGGSCYWFFD (“HC”) amino acid sequence

L WGRGTLVTVSS

Ab 675 1350 DIRLTQSPSSLSASVGDRVTITC RASQTINAYLN WYQQRPGKAPNLLIY AASSLQS GV ADI-41378 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYKTAYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 676 1351 QVQLVQSGAEVKKPGESLKISCKGSG YSFSSFWIG WVRQMPGKGLEWMG IIYPGD ADI-41379 Heavy chain variable region

SDTRYSPSFKG QVTISADTSISTAYLQWSSLKASDTAMYYC AKSIVGSTGSFDP WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 676 1352 DIQMTQSPSSLSASVGDRVTITC QASQDISNFLN WYQQKPGKAPKLLIY DASNLRT ADI-41379 Light chain variable region

GVPSRFSGSGSGTEFTFTISSLQPEDIATYYC QQYHDLPPLT FGGGTKVDIK (“LC”) amino acid sequence

Ab 677 1353 QVQLVQSGAEVKKPGESLKISCKGSG YSFTSYWIG WVRQMPGKGLEWMG IIYPGD ADI-41380 Heavy chain variable region

SDTRYSPSFQG QVTISADKSISTAYLQWSSLKASDTAMYYC ASSRAYYDILTGYYVAS (“HC”) amino acid sequence

AETQTKAAFDI WGQGTTVTVSS

Ab 677 1354 DIQVTQSPSSLSASVGDRVTITC QASQDISNYLN WYQQKPGKAPKLLIY DASNLET G ADI-41380 Light chain variable region

VPSRFSGSGSGTDFSFTISSLQPEDIATYYC QQYDNLIT FGQGTKVEIK (“LC”) amino acid sequence

Ab 678 1355 QVQLQESGPGLVKPSQTLSLTCTVSG DSISGGEHYWS WIRQPPGKGLEWIG SIYYS ADI-41381 Heavy chain variable region

GTTYYNPSLKS RLTVSVDTFKNQFSLMLSYVTAADTAVYYC ARDASPAYHDYIWGS (“HC”) amino acid sequence

CRYFDK WGQGTLVTVSS

Ab 678 1356 EIVLTQSPGTLSLSPGERATLSC RASQSVSSNYLA WYQQKPGQAPRILIH GASSRAT G ADI-41381 Light chain variable region

IPDRFSGSGSGTDFTLTVSRLEPEDFAVYYC QQYGSTPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 679 1357 EVQLVESGGGLVQPGRSLRLSCAASG FTFDDYAMH WVRQAPGKGLEWVS GISWS ADI-41382 Heavy chain variable region

GDTRGYAESVKG RFTITRDNAKKYLYLQMNSLRAEDTAFYYC AKDAYYFGSGNEKF (“HC”) amino acid sequence

YYGMDV WGQGTTVTVSS

Ab 679 1358 DIVLTQTPATLSVSPGERATLSC RASQNVISNLA WYQQKPGQAPRLLIY GASTRAT GI ADI-41382 Light chain variable region

PARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPQT FGQGTKVEIK (“LC”) amino acid sequence

Ab 680 1359 QVQLVQSGAEVKKPGSSVRVSCKASG GTFSRYAIS WVRQAPGQGLEWMG GVIPR ADI-41384 Heavy chain variable region

FDKTNYAQKFQG RVMITADKSTSTAYMELSSLRSDDTAVYYC AGDRLDTKITHTWY (“HC”) amino acid sequence

GFGDF WGQGTTVTVSS

Ab 680 1360 EIVLTQSPGTLSLSPGERATLSC RASQSVTSNFLA WYQQRPGQAPRLLIY GASVRAI D ADI-41384 Light chain variable region

IPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDPFRT FGQGTKVEIK (“LC”) amino acid sequence

Ab 681 1361 EVQLVESGGGVVQPGRSLRLSCAASG FTFSSYGMH WVRQAPGKGLEWVA VIWYD ADI-41385 Heavy chain variable region

GNNEKYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARPTQKYSSSWYW (“HC”) amino acid sequence

EDSIDY WGQGTLVTVSS

Ab 681 1362 QSVLTQPPSVFGAPGQRVTISC TGSSSNIGAGYPVH WYQQLPGTAPKLLIY GNSNR ADI-41385 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGGVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 682 1363 QVQLVQSGAEVKKPGASVKVSCKASG YTFTGNYIH WVRQAPGQGLEWMG GINP ADI-41386 Heavy chain variable region

NSGATNYARKFQ GRISMTRDTSINTAYMEVSSLRSDDTATYYC ARDAPPVVIPAAIH (“HC”) amino acid sequence

WFDA WGQGTLVTVSS

Ab 682 1364 SYELTQPPSASGTPGQRVTISC SGSSSNIGRNTVN WYQQFSGTAPRLLIY RTNQRPS ADI-41386 Light chain variable region

GVPDRFSGSKSGTSASLVISGLQSEDEADYYC ASWHDTLNDVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 683 1365 EVQLVESGGGVVQPGRSLRLSCAASG FTFSNYAIH WVRQAPGKGLEWVA AISYDG ADI-41389 Heavy chain variable region

GNKFYADSVKG RFTISRDNSRNTLYLQMNSLRPEDTAVYYC ARDRWELNYGIDV W (“HC”) amino acid sequence

GQGTTVTVSS

Ab 683 1366 SYELMQPPSVSVSPGQTARITC SGDALPKQYAY WYQQKPGQAPVLVIY KDSERPS G ADI-41389 Light chain variable region

IPERFSGSTSGTTVTLTISGVQAEDEADYYC QSADSSSTFFYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 684 1367 EVQLVESGGGLVKPGGSLRLSCAASG FSSSSYFMN WVRQAPGKGPEWVS SISGSSS ADI-41390 Heavy chain variable region

FINYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARAVLPAGVGGYWFDS (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 684 1368 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQHLPGRAPKLLIY GNSNR ADI-41390 Light chain variable region

PS GVPDRFSGSKSGTSASLVITGLQAEDEADYCC QSYDSSLSGAV FGGGTQLTVL (“LC”) amino acid sequence

Ab 685 1369 EVQLLESGPGLVKPSETLSLTCTVSG GSISGYYWS WIRQPPGKGLEWIG YIYHSGGST ADI-41391 Heavy chain variable region

NYNPSLKS RVTISVDTSKNQFSLKVSSVTAADTAVYYC ARLARVVTTFDF WGQGAL (“HC”) amino acid sequence

VTVSS

Ab 685 1370 QPVLTQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQKPGTAPKLMIF DVSNR ADI-41391 Light chain variable region

PS GVSNRFSGSKSDNTASLTISGLQAEDEADYYC SSYTSSTNLV FGGGTKLTVL (“LC”) amino acid sequence

Ab 686 1371 EVQLVESGGGVVQPGGSLRLSCAASG FEFRDYAMH WVRQAPGKGLEWVA LISYD ADI-41392 Heavy chain variable region

GSKIHYADSVQG RFSISRDNSKNSLYLQMNSLRSEDSAKYYC VQDHWLVPAF WGQ (“HC”) amino acid sequence

GAQVTVSS

Ab 686 1372 QPVLTQPASVSGSPGQWITISC TGTSSDIGYYDYVS WYQQYPGKAPKLIIY EVSHRPS ADI-41392 Light chain variable region

GVSNRFSGSKSGNTASLSISGLQAEDEADYYC SSYTTSNAGV FGTGTKLTVL (“LC”) amino acid sequence

Ab 687 1373 QVQLVQSGAEVKKPGESLKISCKGSG YSFTSYWIG WVRQMPGKGLEWMG IIYPGD ADI-41393 Heavy chain variable region

SDTRYSPSFQG QVTISADKSTSTAYLQWSSLKASDSAMYYC ARSEFSSSFDF WGQG (“HC”) amino acid sequence

TLVTVSS

Ab 687 1374 NFMLTQPHSVSESPGKTVTISC TGSSGSIASYYVQ WYQLRPGSAPTTVIY EDNQRLS ADI-41393 Light chain variable region

GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYRSGIPWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 688 1375 QVQLVQSGAEVKKPGSSVKVSCKASG GTFNTYAIS WVRQAPGQGLEWMG GIIPIL ADI-41394 Heavy chain variable region

GVSNYAQRFQG RVTFSADELTNTAYMELSSLRSEDTAVYFC ARPVGAYTLGDAFEI (“HC”) amino acid sequence

WGRGTTVTVSS

Ab 688 1376 QPVLTQSSSASASLGSSVKLTC TLSSGHSDFIIA WHQQQPGKAPRYLMK FEGNGRY ADI-41394 Light chain variable region

SKGS GIPDRFSGSSSGADRCLTISNLQSEDEADYYC ETWDSNTHVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 689 1377 EVQLVESGGGLVNPGGSLRLSCVVSG FAFSSYGMN WVRQAPGKGLEWVS SISASS ADI-41396 Heavy chain variable region

SYIDYADSVKG RFIISRDNAKNSLHLQMNSLRAEDTAVYYC ARLGYDSSTYYTNWFD (“HC”) amino acid sequence

P WGRGTLVTVSS

Ab 689 1378 QSVVTQEPSVSGAPGQRVTISC TGSSSNIGTGYDVH WYQQLPGAAPKLLIY GNSNR ADI-41396 Light chain variable region

PS GVPDRISGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 690 1379 EVQLVESGGGLVKPGGSLRLSCAASG FKFSSYYLN WVRQAPGKGLEWVS SISGGSS ADI-41397 Heavy chain variable region

YINYADSVKG RFTISRDNAKNTLDLQMSNLRAEDTAVYYC ARVVGATGPLYFDL WG (“HC”) amino acid sequence

RGTLVTVSS

Ab 690 1380 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQFPGTAPKLLIY GNNNR ADI-41397 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYCQ SYDSSLSGYV FGAGTKVTVL (“LC”) amino acid sequence

Ab 691 1381 EVQLLESGAEVKKPGASVKVSCKASG YTFTNYGIS WVRQAPGQGLEWMG WISAY ADI-41398 Heavy chain variable region

NGNTNYAQKLQG RVTMTTDTSTSTAYMELRSLRSDDTAVYYC ARDGGVIAAATLG (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 691 1382 EIVLTQSPLSLPVTLGQPASISC RSSQSLVYSDGNTYLS WFQQRPGQSPRRLIY KISNR ADI-41398 Light chain variable region

DS GVPNRFSGSGSGTDFTLKISRVEAEDVGIYYC MQGIYWPPT FGQGTKVEIK (“LC”) amino acid sequence

Ab 692 1383 QVQLVQSGAEVKKPGASVKVSCKASG YTFTTFAIH WVRQAPGQRLEWMG WINA ADI-41399 Heavy chain variable region

GNGNTKYSQKFQG RVTITRDTSASTAYMELSSLRSEDTAVYYC ARPEISSSSLNEKDD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 692 1384 QPVLIQPASVSGSPGQSITISC TGTSSDVGAYDFVS WYQQHPGKAPKFMIY EVSHR ADI-41399 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTTSNTLV FGGGTKLTVL (“LC”) amino acid sequence

Ab 693 1385 EVQLLESGGGLIQPGGSLRLSCAASK FTFSDYEMN WVRQAPGKGLEWLS YISSSGGI ADI-41400 Heavy chain variable region

MYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYFC ARAGRLLSGLDV WGHG (“HC”) amino acid sequence

TTVTVSS

Ab 693 1386 EIVLTQSPSTLSASVGDRVTITC RASQSISPWLA WYQQKPGKAPKLLIY RASSLET GV ADI-41400 Light chain variable region

PPRFSGSGSGTEFTLTISSLQPDDFATYYC QHYNSYLYS FGQGTKVEIK (“LC”) amino acid sequence

Ab 694 1387 EVQLLESGGGLVHPGRSLRLSCAASG FTFGDYAMH WVRQAPGKGLEWVS GISWN ADI-41401 Heavy chain variable region

SDTIEYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTALYYC AKDFGSSWEAYFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 694 1388 DIVLTQSPSYLSASVGDRVTITC RASQSISTYLN WYQQKPGKAPKLLIS AASSLQS GVT ADI-41401 Light chain variable region

SRFSGSGSGTDFSLTISSLQPEDFATYYC QQSYSTALT FGGGTKVEIK (“LC”) amino acid sequence

Ab 695 1389 EVQLVESGGGLVKPGGSLRLSCAASG FTFGTYTMN WVRQAPGKGLEWVS SISSSSS ADI-41403 Heavy chain variable region

HIYYADSVKG RFTISRDNARKALYLQMNSLRPEDTAVYFC ARFLGDYGGDGNTYYY (“HC”) amino acid sequence

YYGMDV WGQGTTVTVSS

Ab 695 1390 EIVMTQSPLSLPVTPGEPASISC RSSQSLLHSNGKNYLD WYLQKPGQSPQLLIH LGS ADI-41403 Light chain variable region

NRAS GVPDRFSGSGSGTDFTLQISRVEAEDVGVYYC MQALQTPT FGGGTKLEIK (“LC”) amino acid sequence

Ab 696 1391 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYGIS WVRQAPGQGLEWMG GIIPIF ADI-41404 Heavy chain variable region

GTVSYAQKFRG RLTITAHEPTSTAYMDLSSLRSEDTAVYYC ARINGRGWELSSLNYY (“HC”) amino acid sequence

YGMDV WGQGTTVTVSS

Ab 696 1392 EIVLTQSPGTLSLSPGERGTLSC RASQSVASSYLA WYQQKPGQAPRLLIY GATSRAT G ADI-41404 Light chain variable region

IPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSLFT FGGGTKVDIK (“LC”) amino acid sequence

Ab 697 1393 EVQLLESGGGLVQPGGSLRLSCAASG FSFSIYSMN WVRQAPGKGLEWIS YITSTGSP ADI-41405 Heavy chain variable region

TYYADSVKG RFTISRDNAKNSLYLQMSSLRAEDTAVYYC VTYCSSSSCPAEFDY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 697 1394 EIVLTQSPATLSLSPGERATLSC RASQSVNSYLA WYQQKPGQAPRLLIY DASNRAT GI ADI-41405 Light chain variable region

PARFSGSGSGTDFTLTISSLEAEDFAVYYC QHRNNWPALT FGGGTKVEIK (“LC”) amino acid sequence

Ab 698 1395 EVQLVESGGNLVQPGGSLRLSCAASG FTFSSYVMN WVRQAPGKGLEWVS GISGS ADI-41406 Heavy chain variable region

GGTSYYADSVKG RFTISRDNSNNTLYLQMKSLRAEDTAVYYC AKDPRFQKWLIEGT (“HC”) amino acid sequence

NWFDS WGQGTLVTVSS

Ab 698 1396 DIQVTQSPSSLSASVGDRVTITC RASQDVSNYLA WFQQKPGTAPKSLIY AASILQS G ADI-41406 Light chain variable region

VPSKFRGSGSGTDFSLTISSLQPEDFATYYC QQYRSFPPT FGGGTKVEIK (“LC”) amino acid sequence

Ab 699 1397 EVQLVESGGGLVQPGGSLRLSCAASG FTFSSNAMS WVRQAPGKGLEWVS YISGGS ADI-41407 Heavy chain variable region

ATKSYADSVKG RFTISRDNSKNTLYLQMKSLRAEDTAVYYC VGGSAYYSGFDY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 699 1398 DIVMTQSPSSLSASVGDRVTISC RASQDIRNYLA WYQQKPGKVPNLLIY AASTLES G ADI-41407 Light chain variable region

VPSRFSGSGYGTDFTLTISGLQPEDVATYYC QKYDSAPPFT FGPGTKVDIK (“LC”) amino acid sequence

Ab 700 1399 QVQLVESGAEVKKPGESLKISCRDSG YSFSSFWIG WVRQMPGKGLEWVG IIYPGDS ADI-41408 Heavy chain variable region

DIRYSPSFQG RVTISADKSISTAYLQWRSLKASDSAMYYC ARSEKLGSFDR WGQGTL (“HC”) amino acid sequence

VTVSS

Ab 700 1400 DIQMTQSPSSLSASVGDRVTITC QANRDISNCLN WYQQRPGKAPELLIY DASYLET G ADI-41408 Light chain variable region

VPSRFTGSGSGTDFTFTISSLQPEDIATYYC QQYDNLLFT FGPGTKVEIK (“LC”) amino acid sequence

Ab 701 1401 QVQLVQSGAEVKKPGASVKVSCKASG YTFTNYGIS WVRQAPGQGLEWMG WISA ADI-41409 Heavy chain variable region

YNGNTNYAQKFQD RVTMTTDTSTSTAYMELRSLRYDDTAVYYC ARDTPGEYASA (“HC”) amino acid sequence

MFDH WGQGTLVTVSS

Ab 701 1402 DIVMTQSPLSLPVTLGQPASISC RSSQSLVYSDGNTYLS WFQQRPGQSPRRLIY KVS ADI-41409 Light chain variable region

NRDS GVPDRFSGSGSGTDFTLKISGVEAEDVGVYYCM QGTHWPPT FGQGTKLEIK (“LC”) amino acid sequence

Ab 702 1403 EVQLLESGGGLAQPGRSLKVSCAASG VTVTSTYMG WVRQAPGKGLQWVS VIYSD ADI-41414 Heavy chain variable region

GTTYYADSVKG RFTISRDHYKNTLYLQMNSLRAEDTALYYC ARGNRRTDFGY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 702 1404 EIVMTQSPSTLSASVGDRVTITC RASQTISNWLA WYQQKPGKAPKLLIY QASTLES G ADI-41414 Light chain variable region

VPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQYNTYYT FGPGTKVEIK (“LC”) amino acid sequence

Ab 703 1405 QVTLKESGPALVKPTQTLTLICTFSG FSLSTSRTRVS WIRQPPGKALEWLA RVDWD ADI-41415 Heavy chain variable region

DDKFYNPVLKT RLSISKDPSKNQVVLTMTNVDPVDTATYYC VRMAHYGSGGYYVE (“HC”) amino acid sequence

YFQD WGQGTLVTVSS

Ab 703 1406 DIQLTQSPASLSASAGDRVTITC RASQNINRYLN WYQQQSGKAPKLLIY AASILQS G ADI-41415 Light chain variable region

VPSRFSGSGSGTDFTLTITSLQPEDFAIYYC QQSYTTPKYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 704 1407 EVQLVESGGGLVKPGGSLRLSCAASG FKFSSYTMN WVRQAPGKGLEWVS SITGGS ADI-41416 Heavy chain variable region

SFINYADSVKG RFTISRDNAKNSLYLQMVSLRAEDTAVYYC ARDLSSHITIFGAVSDY (“HC”) amino acid sequence

WGRGTTVTVSS

Ab 704 1408 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDAH WFQQLPGSAPKLLIY ANTNR ADI-41416 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSTLSVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 705 1409 QVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISAGS ADI-41417 Heavy chain variable region

SYIYYADSLKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARVNTHYYDSSAYHNF (“HC”) amino acid sequence

DS WGQGTLVTVSS

Ab 705 1410 QPVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNTNR ADI-41417 Light chain variable region

PS GVPERFSGSKSGTSASLAITGLQAEDEADYYC QSYDTNLSAPWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 706 1411 EVQLVESGGGLVKPGGSLRLSCAASG LSFTDAWMG WVRQAPGKGLEWVG HIKKK ADI-41418 Heavy chain variable region

TDYGPTAYAAPVRG RFTVSRDDSKNTLYLQMTSLKTEDTAVYYC ITERGYNFGYND (“HC”) amino acid sequence

YFGVDV WGQGTLVTVSS

Ab 706 1412 QPGLTQPPSVSVSPGQTARITC SGDALPKKYAY WYQQKSGQAPVMIIY EDNKRPSG ADI-41418 Light chain variable region

IPERFSGSTSGTMATLTISGAQMEDEADYYC FSTDSGDDQSGV FGGGTRLTVL (“LC”) amino acid sequence

Ab 707 1413 EVQLVESGGGLVQPGRSLRLSCAASG FTFDDYAMH WVRQAPGKGLEWVS GISW ADI-41419 Heavy chain variable region

NSGSVGYSDSVKG RFTISRDNAKSSLYLQMNNLRAEDTALYYC ARDMAHTQDYFD (“HC”) amino acid sequence

TSEYDS WGQGTLVTVSS

Ab 707 1414 QPVLTQPASVSGSPGQSITISC TGTSSDIGAYNYVS WYQQHPGKAPKLVVY EVNNR ADI-41419 Light chain variable region

PS GISNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTVSATLV FGGGTKLTVL (“LC”) amino acid sequence

Ab 708 1415 EVQLLESGGGVVQPGRSLRLSCAASG FTFSSYAMH WVRQAPGKGLEWVA VISYDG ADI-41420 Heavy chain variable region

SNKYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARVPCSSTSCYTTDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 708 1416 QPVLTQPPSVSGSPGQSVTISC TGTSSDVGSYNRVS WYQQPPGTAPKLMIY EVSNR ADI-41420 Light chain variable region

PS GVPDRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSPV FGGGTKVTVL (“LC”) amino acid sequence

Ab 709 1417 QVQLVESAAEVKRPGASLKVSCKASG YTFIDYDIS WVRQAPGQGLDWMG WISTY ADI-41421 Heavy chain variable region

DGSAKYPENLQA RVAMTTDTSTSTAYMELESLTSDDTAVYYC ARARRGSSGWVST (“HC”) amino acid sequence

TGPTPFFDY WGRGTLVTVSS

Ab 709 1418 SYELTQPPSVSVSPGQTARITC SGDALPKRYAY WYQQKSGQAPVLVIY EDNKRPS GI ADI-41421 Light chain variable region

PERFSGSSSGTVATLTISGAQVEDEADYSC YSTDATGNHRGL FGGGTKLTVL (“LC”) amino acid sequence

Ab 710 1419 QVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-41423 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDPSSSWNRNDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 710 1420 QSVLIQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY DVSNR ADI-41423 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSTLVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 711 1421 QVQLVQSGAEVREPGASVKVSCKPSG YTFANYGIS WVRQAPGQGLEWMA WISAY ADI-41424 Heavy chain variable region

NGNTNYAPKVQG RVSVTTDSSTGIGYMELRSLRSDDTAVYYC VRDTPAIAGAATLD (“HC”) amino acid sequence

F WGQGTLVTVSS

Ab 711 1422 DIVLTQSPLSLAVTPGQSASISC RSRQSHVFSDGNTYVS WFQQRPGRSPRRLIY RVSY ADI-41424 Light chain variable region

RDS GVPDRFSGSGSGSDFTLRISRVEAEDVGVYYC MQGTHWPRT FGQGTKLEIK (“LC”) amino acid sequence

Ab 712 1423 EVQLLESGPAVVKPTQTLTLTCTVSG LSLSSPRMSVS WIRQPPGKGLEWLA RIDWD ADI-41425 Heavy chain variable region

GDKYYGTSLKT RLSISKDTSKNQVVLTMTNMDPVDTGTYYC AQTSIYASNAYYLARL (“HC”) amino acid sequence

DP WGQGMLVTVSS

Ab 712 1424 EIVMTQSPSLLSASVGDRVTITC RASQNIATYLN WYQQKPGKAPRLLIY AASNLQS G ADI-41425 Light chain variable region

VPSGFSGSGSGTVFTLTISSLQPEDFATYFC QQSYETSLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 713 1425 QVQLVESGPGLVKPSETLSLTCTVSG GSIGGYYWS WIRQPPGKGLEWIG YMYYSGS ADI-41427 Heavy chain variable region

TNYNPSLKS RVIMSVDTSKNQFSLKLTSVTAADTAVYYC ARVLRFLVGGMDV WGQ (“HC”) amino acid sequence

GTTVTVSS

Ab 713 1426 QSVLIQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLIIY EVSNRPS ADI-41427 Light chain variable region

GVSNRFSGSKSGNTASLTISGLQAEDEADYYC NSYTTIATLV FGTGTKVTVL (“LC”) amino acid sequence

Ab 714 1427 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYAIS WVRQAPGQGLEWMG GIIPIF ADI-41429 Heavy chain variable region

GTVNYAQKFPG RVTITADESTSTAYMELSSLRSEDTAIYYC ARDSPSYTGSLLFSQYYY (“HC”) amino acid sequence

GMDV WGQGTTVTVSS

Ab 714 1428 QPVLTQPASVSGSPGQSITISC TGTSSDVGGYDYVS WYQHHPGKAPKLMIY EVSNR ADI-41429 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSFTTSSPRV FGTGTKLTVL (“LC”) amino acid sequence

Ab 715 1429 QVQLVQSGAEVKKPGASVRVSCTASG YRFFTYGIT WVRQAPGQGLEWMG WISAY ADI-41431 Heavy chain variable region

NGNTKFAQKFQG RLTMTTDAPTSTADMELRGLRSDDTAVYYC AREEGGYHGTGS (“HC”) amino acid sequence

NNY WGQGTLVTVSS

Ab 715 1430 QSVLTQPPSVSAAPGQKVTISC SGSGSNVGGNDVS WYQQFPGTAPKLLIY DNSKRP ADI-41431 Light chain variable region

S GIPDRFSGSKSGTSATLVITGLQTGDEADYYC GTWDSSLSVGV FGTGTKLTVL (“LC”) amino acid sequence

Ab 716 1431 QVQLVQSGAEVKKPGYSVKVSCKASG GTFSTFGIS WVRQAPGLGLEWMG GIIPLF ADI-41432 Heavy chain variable region

GTADYSKKYQG RVTITADESTSTGYMELNSLTPEDTAVYYC ARSPGHLWSRYDAFE (“HC”) amino acid sequence

V WGQGTTVTVSS

Ab 716 1432 QPVLTQPRSVSGSPGQSVTISC SGTSSDVGGYNYVS WYQQYPGKAPKLIIY DVNKR ADI-41432 Light chain variable region

PS GVPDRFSGSKSDNTASLTISGLQADDESDYFC CSYAGSHTFEV FGTGTKVTVL (“LC”) amino acid sequence

Ab 717 1433 EVQLLESGGGAVQPGRFLRLSCAASG FTFRSYGMH WVRQAPGKGLEWVA VISYD ADI-41433 Heavy chain variable region

GSDKYYADSVKG RFTISRDNSKNTLFLLMNGLRAEDAAVYYC AKDIASAGTLRGSDV (“HC”) amino acid sequence

WGQGTMVTVSS

Ab 717 1434 QPVLTQPRSVSGSPGQSVTISC TGTSSDVGGFNYVS WYQQHPGKAPKLMIY DVRV ADI-41433 Light chain variable region

RPS GVPDRFSGSKSGNTASLTISGLQGEDEADYYC CSYTVTYTLV FGGGTKLTVL (“LC”) amino acid sequence

Ab 718 1435 EVQLVESGGGLVQPGRSLRLSCEASG FTFDDYAMH WVRQTPGKGLEWVS GISWN ADI-41434 Heavy chain variable region

SGSIVYADSVKG RFTISRDNAKNSLYLQMHSLRPEDTALYYC AKDNYTFGNYYYYYG (“HC”) amino acid sequence

MDV WGQGTTVTVSS

Ab 718 1436 EIVLTQSPVTLSVSPGERATLSC RASQNVISNLA WYQQKPGQAPRLLIY GASTRAT GI ADI-41434 Light chain variable region

PARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPLS FGGGTKVEIK (“LC”) amino acid sequence

Ab 719 1437 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSLN WVRQAPGKGLEWVS SISSSGTY ADI-41435 Heavy chain variable region

IFYADSVKG RFTISRDNAKDSLFLQMNSLRAEDTAVYYC ARARDMGNYDILTGYYR (“HC”) amino acid sequence

VDAFDI WGQGTMVTVSS

Ab 719 1438 QSVLTQPPSASKTPGQRVTISC SGSSSNIGGNTVN WYQQLPGTAPKLLIY TNDQRPS ADI-41435 Light chain variable region

GVPDRFSGSKSGTSASLAISGLQSEDEADYYC AAWDDSLNGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 720 1439 EVQLLESGGGVVQPGRSLRLSCAASG FTFSDYAMH WVRQAPGKGLEWVA LISFDG ADI-41436 Heavy chain variable region

SNEYYADSVKG RFTISRDNSRNTVYLQVNTLRPDDTAVFYC ARDSHLRLTTRGWGS (“HC”) amino acid sequence

FDY WGQGTLVTVSS

Ab 720 1440 NFMLTQPHSVSESPGKTVTIAC TRSSGSIARNYVQ WYQQRPGRSPTMVIY EDNQR ADI-41436 Light chain variable region

PS GVPDRFSGSIDTSSNSASLTISGLKTEDEADYYC QPYDPDNLV FGGGTKLTVL (“LC”) amino acid sequence

Ab 721 1441 QVQLVQSGGEVKKPGASVKVSCKASG YTFTHYGIS WARQAPGQGIEWMG WINV ADI-41437 Heavy chain variable region

HNGNTEYAQRFQ GRVTMTTDTSTNTAYMEMTSLTSDDTAVYYC ARDKIVVVVVP (“HC”) amino acid sequence

NYHGMDV WGQGTLVTVSS

Ab 721 1442 EIVLTQSPDSLAVSLGERATINC KSSQSVLYRANNRNYLA WYQQKPGQPPKLLIY WA ADI-41437 Light chain variable region

STRES GVPDRFSGSGSGTDFTLTISSLQAEDVALYYC HQYHSSPRT FGQGTKVDIK (“LC”) amino acid sequence

Ab 722 1443 QVQLVQSGAEMRRPGSSVRLPCKASG YTFVSHTIV WVRQAPGQGLEWMG GIIPS ADI-41438 Heavy chain variable region

LRTPNYAQNFQD RLTITADESARTAYMELSSLTSNDTAVYYC ARETFQGGYYLDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 722 1444 EIVMTQSPGTLSVSPGDTAALSC RASQSVGRNLA WYQQKPGQAPRLLIF GASTRAA ADI-41438 Light chain variable region

DIPGRFSGSGSGTEFTLTITSLQSEDFAVYYC QQYNKWPPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 723 1445 QVQLVQSGTEVKNPGASVKVSCKASG YTFSNYGIT WVRQAPGQGLEWMA WISAY ADI-41439 Heavy chain variable region

NGNILYAQNVQG RVTMTTDTSTSTGYMELRSLRSDDTAVYYC ARDAPAGTLILLDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 723 1446 DIVMTQTPLSLPVTLGQPASISC RPSQSLVYSDGNTYLN WFQQRPGQSPRRLIY KVS ADI-41439 Light chain variable region

NRDS GVPDRFSGSGSGTDFTLRISRVEAEDVGVYYC MQGSHWPYA FGQGTKVEIK (“LC”) amino acid sequence

Ab 724 1447 EVQLVESGGGLVKPGGSLRLSCAVSG FTFSDYTMN WVRQAPGKGLEWVS SISGSG ADI-41440 Heavy chain variable region

TYIYYGDSVKG QFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARELPAKTIFGVDFLG (“HC”) amino acid sequence

GTTAYDC WGQGTPVTVSS

Ab 724 1448 EIVLTQSPATLSVSPGERATLSC RASQSVSSNLA WYQQKPGQAPRLLIY SATTRAT G ADI-41440 Light chain variable region

VPARFSGSGSGTEFTLTISSLRSEDFAVYYC QQYNNGGT FGPGTKVEIK (“LC”) amino acid sequence

Ab 725 1449 EVQLVQSGPGLVKPSETLSLICSVSG ASISRYHYYWG WIRQSPGKGLEWIG TIYYSG ADI-41441 Heavy chain variable region

TTYYNPSLES RVTISADTSKNQVSLKLTSVTAADTAVYYC ARGSGDTALDFSFEY WG (“HC”) amino acid sequence

QGALVTVSS

Ab 725 1450 DIQLTQSPSFLSASVGDRITITC RASQGISNSLA WYQQKPGKAPKLLIY AASTLQF AV ADI-41441 Light chain variable region

PSRFSGSGSGTEFTLTISSLQPEDFATYYC QQLDSYPLT FGGGTKLEIK (“LC”) amino acid sequence

Ab 726 1451 EVQLLESGGGLVQPGRSLRLSCAASG FTFDDYAMH WVRQAPGKGLEWVS GISWH ADI-41442 Heavy chain variable region

SGSIVYADSVKG RFTISRDNAKNSLYLQMSSLRAEDTALYYC VKDHYNWNDNPHFH (“HC”) amino acid sequence

YGLDV WGQGTTVTVSS

Ab 726 1452 EIVLTQSPATLSVSPGERATLSC RASQSVISNLA WYQQKPGQAPRLFIY GASTRAT GI ADI-41442 Light chain variable region

PARFSGSGSGTEFTLTISSLQSEDFAVYFC QQYNNWPIT FGQGTRLEIK (“LC”) amino acid sequence

Ab 727 1453 EVQLVESGGGVVQPGKSLRLSCAASG FTFSSYAMH WVRQAPGKGLEWVS VIWYE ADI-41443 Heavy chain variable region

DSDKYYGDSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARKSGGFGGLDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 727 1454 DIVMTQSPLSLPVTPGEPASISC KSSQSLLTANGYNYLD WYVQKPGQSPHVLIS LGS ADI-41443 Light chain variable region

NRAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQAIETPIT FGQGTRLEIK (“LC”) amino acid sequence

Ab 728 1455 EVQLVESGPRLVKPSQTLSLTCTVSG GSIGTGDYHWT WIRQSPGKGLEWIG NIYYN ADI-41444 Heavy chain variable region

GRTFYNPSLKG RGSISRDASKNQFSLNLSSVSAADTAVYYC ARDRAAKGFDH WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 728 1456 DIQLTQSPSTLSASVGDRVTITC RASQNINGWLA WYQQKPGRVPKLLIY KASTLES G ADI-41444 Light chain variable region

VPSRFSGSASGTEFTLTINNLLPDDFATYYC QQYNDYPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 729 1457 QVQLVQSGAEVKRPGSSVKVSCKAFG GSFSNYAIN WVRQAPGQGLEWMG GISPV ADI-41445 Heavy chain variable region

LGTAIYAKRFQG KVTITADKFANTAYMDLSSLRFEDTAVYYC ARSPPHVEFPLTKWF (“HC”) amino acid sequence

DP WGQGTLVTVSS

Ab 729 1458 EIVMTQSPGTLSLSPGERATLSC RASQSVNSGYLA WYQHKPGRAPRLLIY GASNRAT ADI-41445 Light chain variable region

GVPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYDNSLFT FGPGTKVDIK (“LC”) amino acid sequence

Ab 730 1459 EVQLLESGGGLVQPGGSLRLSCAASG FTYYSYAMN WVRQAPGKGLEWVS AISGG ADI-41446 Heavy chain variable region

GDNTFYAESVKG RFTISRDNAKNTLYLQMDSLRAEDTAVYYC AKDLQGYTSLYCFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 730 1460 EIVMTQSPATLSLSPGERAALSC RASQSVFNYVA WYQQKPGQAPRLLIY DTSKRAT ADI-41446 Light chain variable region

GIPARFSGSGSGTDFTLTISSLEPEDFAVYYC QHRYNWPGLI FGGGTKVEIK (“LC”) amino acid sequence

Ab 731 1461 EVQLLESGGGLVQPGGSLRLSCAASG FTFSTYAMN WVRQAPGKGLEWVS TISGSG ADI-41447 Heavy chain variable region

GSTYYGDSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKAPTPWCSGGSCYV (“HC”) amino acid sequence

SY WGQGTLVTVSS

Ab 731 1462 DIVMTQTPGTLSLSPGERGTLSC RASQSVSSSYLA WYQQKPGQAPRLLIY GASSRAT ADI-41447 Light chain variable region

GIPDRFGGSGSGTDFTLTISTLEPEDFAVYYC QQYQSSPWT FGQGTKLEIK (“LC”) amino acid sequence

Ab 732 1463 TVQLVESGAEVKSPGSSVRVSCQASG GSSNSYAIS WVRQAPGQGLEWMG MISPLF ADI-41448 Heavy chain variable region

GTTRFSQRFQG RVTITADKSTSTAYMELSSLNSEDTALYYC ARGRFDFWSGPTRFYY (“HC”) amino acid sequence

TMDV WGQGTMVTVSS

Ab 732 1464 QSVLIQPASVSGSPGQSITISC SGTSSDIGGYNYVS WYQQHPGKAPKLLIS DVTDRPS ADI-41448 Light chain variable region

GISDRFSGSKSGTSASLTISGLQADDEADYYC TSYTTSSTWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 733 1465 EVQLVESGGGLVKPGGSLRLSCAASG FSFSSYRVN WVRQAPGKGLEWVS SITGGSS ADI-41449 Heavy chain variable region

FIDYADSVKG RFTISRDNAKNSLFLQMNSLRAEDTAVYFC ARDSMTTVTNSLAFDI (“HC”) amino acid sequence

WGQGTMVTVSS

Ab 733 1466 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGVGYDVQ WYQQLPGTAPKLLIY SNNKR ADI-41449 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDRSLSVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 734 1467 EVQLVESGGGLVKPGGSLRLSCAASG FAFSSYGIN WVRQVPGKRLEWVS SISGGSS ADI-41450 Heavy chain variable region

FINYADSVKG RFTISRDNAGNSVYLQMNSLRAEDTAVYFC ARESYGSGSSLNWFDP (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 734 1468 QSVLTQPPSVSGAPGQRVTISC TGSGSNIGAGYDVH WYQQLPGIAPRLVIF GNRNR ADI-41450 Light chain variable region

PS GVPDRISGSKSDTSASLAITGLQAEDEGDYYC QSYDKRLSGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 735 1469 EVQLVESGGGLVQPGGSLRLSCAAAG FTFNNYEMH WVRQAPGKGLEWVS CVTSS ADI-41451 Heavy chain variable region

GTATYYADSVKG RFTVSRDNAKKSLQLQMNSLRAEDTAVYYC ARELYLGEDYYYGL (“HC”) amino acid sequence

DV WGQGTTVTVSS

Ab 735 1470 SYELTQPPSVSVSPGQTASISC SGDKLRNKHTC WYQHKSGQSPVLLIY QDNRRPS GI ADI-41451 Light chain variable region

PDRLSGSKSGTTATLTISWTQAMDEAEYYC QAWDSNSAVI FGGGTKLTVL (“LC”) amino acid sequence

Ab 736 1471 QVQLVQSGAELKKPGASVKVSCKASG HTFATYAIH WVRQAPGQSLEWLG WINTA ADI-41452 Heavy chain variable region

NGDTKYSQKFRA TVTIHGDTSANTVYLELSRLRSEDTAVYYC ASPPLVGAINLEF WG (“HC”) amino acid sequence

PGILVTVSS

Ab 736 1472 QSVLTQPASVSGSVGQSITISC TGTSSDVGGYNSVS WYQHHPDKAPKLIIY EVSNRP ADI-41452 Light chain variable region

S GVSHRFSGSKSGNTASLTISGLQAEDEADYYC SSYTTSDTLI FGGGTKVTVL (“LC”) amino acid sequence

Ab 737 1473 QVQLVQSGAEVRKPGASVKVSCKASG YTFSIYDMN WVRQAPGQGLEWMG WM ADI-41453 Heavy chain variable region

NPNSGNTGYAQKFQG RVTMTGDTSISTAYMELSSLTSEDTAVYYC AVMYGDYPGY (“HC”) amino acid sequence

WGQGSLVTVSS

Ab 737 1474 SYELTQPLSVSVALGQTARITC GGNNIGSKSVH WYQQKPGQAPVLVIY RDAKRPS GI ADI-41453 Light chain variable region

PERFSGSNSGNTATLTISGAQAGDEADYYC QVWDSNAWI FGGRTKLTVL (“LC”) amino acid sequence

Ab 738 1475 QVQLVQSGAEVKKPGASVKVSCKASG YTFTHFGIS WVRQAPGQGLEWMG WISIY ADI-41454 Heavy chain variable region

NGNTNYAQKIQ GRATMTTDASTSTAYMELRSLTSDDTAVYYC AREPPSTTAAATSD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 738 1476 DIVMTQSPLSLPVTLGQPASISC RSSQSLVYIEGNTYLS WFQQRPGQSPRRLIY KVSN ADI-41454 Light chain variable region

RDS GVPDRFSGSGSGTDFTLKISRVEAEDVGLYYC MQGTHWPRT FGQGTKLEIK (“LC”) amino acid sequence

Ab 739 1477 QVQLQESGPGLVKPSQTLSLTCSVSE GSVISGDYYWS WIRQSPGKGLEWLG YIHYS ADI-41455 Heavy chain variable region

GSTYYNPSLKS RVTISVDTSKKQFSLKLSSVTAADTAVYYC ARDLGCIGGVCSAYGLE (“HC”) amino acid sequence

HNYYFGMDV WGQGTTVTVSS

Ab 739 1478 EIVLTQSPATLSLSPGERATLSC RASQSVSSYLA WYQQKPGQAPRLLIY TASNRAT GI ADI-41455 Light chain variable region

PARFSGSGSGTDFTLTISSLEPEDFAVYYC QQRSSWPPYT FGQGTKLEIK (“LC”) amino acid sequence

Ab 740 1479 EVQLLESGGGLFHPGGSLTLSCVASG FTLSTYYMH WVRQAPGKGLVWVA RINSDG ADI-41456 Heavy chain variable region

GYTTYADSVKG RFTVSRDNAKNTLYLQMNSLRVEDTAVYYC AREWVEFDS WGQG (“HC”) amino acid sequence

TLVTVSS

Ab 740 1480 NFMLTQPHSVSASPGKTVTISC TRSSGNIASNYVQ WYQQRPGSSPTTVIT EDNQRP ADI-41456 Light chain variable region

S GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDSSTYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 741 1481 EVQLVESGGGLVRPGGSLRVSCAASG FTFIRYDMH WVRQAPGKGLEWVS GIGTA ADI-41457 Heavy chain variable region

GDTYYAASVQG RFTISRENAKNSLYLQMSNLRPGDTAVYYC AGSMAATGIDQ WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 741 1482 EIVMTQSPLTLPVTPGEPASISC RSSQSLLHSNGFTYLD WFLQKPGQSPQLLIF LGSN ADI-41457 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGIYYC MQALQTPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 742 1483 EVQLLESGSGLVKPSQTLSLTCAVSG DSLNSALYSWS WIRQPPGKGLEWIG YIYYSG ADI-41458 Heavy chain variable region

STYYNSSLKS RVTISIDRSKNQFSLNLNSVTAADTAVYYC ASLQTGYSSGWFFDF WG (“HC”) amino acid sequence

PGILVTVSS

Ab 742 1484 EIVLTQSPGTLSLSPGERATLSC RASQSVSRTYLT WYQQKPGQAPRLLIY GASNRAT G ADI-41458 Light chain variable region

IPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSTPL FGQGTKVEIK (“LC”) amino acid sequence

Ab 743 1485 QVQLVESGGGLVQPGGSLRLSCAASG FPFSAYGIN WVRQAPGKGLEWVS YISSTST ADI-41459 Heavy chain variable region

TIKYADSVKG RFTISRDDAKNSLYLQLRSLRPEDTAVYYC AGGVWSGYYIDF WGQG (“HC”) amino acid sequence

TPVTVSS

Ab 743 1486 NFMLTQPQSVSESPGKTVTISC TRSSGSIGSNFVQ WYQQRPGSSPTTVIY EDYQRPS ADI-41459 Light chain variable region

GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDADMMV FGGGTKLTVL (“LC”) amino acid sequence

Ab 744 1487 QVTLKESGPALVKPTQTLTLICTFSG FSLNTRGMCVS WVRQPPGKALEWLA RIDW ADI-41460 Heavy chain variable region

DDDKNYSTSLRT RLTISKDTSRNQVVLAMANMDPVDTATYYC ARCARYDRSGYYV (“HC”) amino acid sequence

WYLDS WGQGTLVTVSS

Ab 744 1488 DIQMTQSPSSLSASVGDRVTITC RASQTIASYLN WYQQKPGKAPKLLIY VASTLQS G ADI-41460 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSLTQWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 745 1489 QVQLVQSGAEVKKPGASVKVSCRASG YTFSSYDIN WVRQATGQGLEWMG WMS ADI-41461 Heavy chain variable region

PNSANTGYAQKFQG RVIMIRDTSINTAYMELSSLSSEDTAVYYC ARFLGYCSGGSC (“HC”) amino acid sequence

YPGYGMDV WGQGTTVTVSS

Ab 745 1490 EIVLTQSPDSLAVSLGERATINC KSSQNVLYSSNNKDYLS WYQQKPGQPPKLLIY WA ADI-41461 Light chain variable region

STRES GVPDRFSGSGSGTDFTLTINSLQAEDVAVYYC QQYYGTPYT FGQGTKLEIK (“LC”) amino acid sequence

Ab 746 1491 QVQLQQWGAGLVKPSETLSLSCDVYG GSFSGYYWT WIRQPPGKGLEWIG EINHS ADI-41462 Heavy chain variable region

GRTNYNPSLKN RVTISVDTSKKQFSLKLSSVTAADTAVYFC ARAPYYDIVTDYNITTA (“HC”) amino acid sequence

YFYGMDV WGQGTTVTVSS

Ab 746 1492 DIQMTQSPDSLAVSLGERATINC RSSQSVLYSSNNKNYLT WYQQKPGQPPKLLIY W ADI-41462 Light chain variable region

ASTRES EVPDRFSGSGSGTDFSLTISSLQAEDVAVYYC QQYYNTPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 747 1493 QVQLVQSGAEVKKPGASVKVSCTASG YSFTDYDIS WVRQAPGQGLEWMG WISAY ADI-41463 Heavy chain variable region

NGNTNYAQKFQD RVTMNTDTSTNTAYMELRGLRSDDTAVYYC ARNCYYGSGTCYI (“HC”) amino acid sequence

EDYYFDY WGQGTLVTVSS

Ab 747 1494 DIQMTQSPSSLSASVGDRVTITC RASQDIKNDLG WYQQKPGKPPKRLIY GASRSQS ADI-41463 Light chain variable region

GVPSRFSGSGSGTDFTLTIYSLQPEDFATYYC LQHSDYPFT FGQGTRLEIK (“LC”) amino acid sequence

Ab 748 1495 QVQLVESGPGLVRPSGTLSLICTVSG DSVNSYRWS WIRQSPGKGLEWIG YISYSGET ADI-41464 Heavy chain variable region

NYNPSLKS RVSISVGTSRYQFFLKLSSVTAADTATYYC ARDKTTIFGVSHYYFGVDV W (“HC”) amino acid sequence

GQGTTVTVSS

Ab 748 1496 DIVMTQTPLSLPVTPGEPASISC RSSQSLLKSDGYNSLD WYLQRPGQSPQLLIY LGSN ADI-41464 Light chain variable region

RAS GVPARFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPFT FGPGTKVEIK (“LC”) amino acid sequence

Ab 749 1497 QVQLVQSGGGVVQPGRSLRLSCAASG FTFTSYDMH WVRQAPGKGLEWVA IISHD ADI-41465 Heavy chain variable region

GSKQFYADSVKG RFTISRDNSKNTLYLQMNSLRPEDTAMYYC AKDTPSWGLLAEFF (“HC”) amino acid sequence

RH WGQGTLVTVSS

Ab 749 1498 EIVLTQSPDSLAVSLGERATINC KSSQSVLYSSNDKDYLA WYQHKPGQPPKLLIY WA ADI-41465 Light chain variable region

STRES GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC QQYYGTPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 750 1499 QVQLVQSGAEVKKPGASVKVSCKASG YTFNFYYMH WVRQAPGQGLEWMG WIN ADI-41466 Heavy chain variable region

PKSGGTSYAQKFQG RVIMTGDTSISTTYMELSRLRSDDTAVYYC ARADTGLELDV W (“HC”) amino acid sequence

GQGTTVTVSS

Ab 750 1500 QSALIQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLILY DVSKRP ADI-41466 Light chain variable region

S GVSNRFSGSKSGNTASLTISGLQAEDESDYFC SSYTRSNTVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 751 1501 EVQLVESGGGLVKPGGSLRLSCAASG FSFSSYNMN WVRQAPGKGLEWVS SISGGS ADI-41467 Heavy chain variable region

SFVNYADSVKG RFTISRDNAKNSLYLQMSSLKAEDTAIYYC ARDPVYCSAASCSAYF (“HC”) amino acid sequence

DS WGQGSLVTVSS

Ab 751 1502 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNNNR ADI-41467 Light chain variable region

PS GVPDRFSGFKSGSSASLAITGLQAEDEADYYC QSYDIGLSDSHVV FGGGTQLTVL (“LC”) amino acid sequence

Ab 752 1503 QVQLQQWGAGPLKSSETLSLTCEVYG GPFSGYSWS WIRQPPGKGLEWIG EINHSG ADI-41468 Heavy chain variable region

STNYNPSLKS RVSFSVDTSKNQFSLKLSSVTAADTAVYYC ARGAGFCTSTSCPPGLYY (“HC”) amino acid sequence

YYGMDV WGHGTTVTVSS

Ab 752 1504 SYELTQPLSVSVALGQTARITC GGNNIESKNVH WYQQMPGLAPVMVIY RDTNRPS ADI-41468 Light chain variable region

GIPERFSGSNSGNTATLTISRAQAGDEADYYC QVWDSGTVI FGGGTKLTVL (“LC”) amino acid sequence

Ab 753 1505 EVQLVESGGGVVQPGRSLRLSCAASG FTFSSYGMH WVRQAPGKGLEWVA VISYD ADI-41469 Heavy chain variable region

GSFIKYADSMMG RFTISRDNSKNTLYLQMSSLRPEDTATYYC AKDALIPEY WGQGT (“HC”) amino acid sequence

LVTVSS

Ab 753 1506 QPVLTQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQKHPDKAPRVIIY EVSNRP ADI-41469 Light chain variable region

S GVSNRFSGSKSGNTASLTISGLQAEDEADYYC CSYTSTSGVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 754 1507 QVQLVQSGADVKKPGSSVKISCKASG GSFITNSLS WVRRAPGQGLEWMG GIIPVS ADI-41471 Heavy chain variable region

GTTTYAQKFLG RVTFTADESTSTAYMELNSLRSEDTAVYYC ARFLGTPYPNVHYGM (“HC”) amino acid sequence

DV WGQGTTVTVSS

Ab 754 1508 DIRVTQSPSSLSASVGARVTITC RASQSISTYLN WYQEKPGKAPKLLIY AASSLQR GV ADI-41471 Light chain variable region

PSRFSGSGSETTFTLTISSLQPEDFATYYC QQSYTAAYN FGQGTKVEIK (“LC”) amino acid sequence

Ab 755 1509 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYAIS WVRQAPGQGLEWMG RIIPVL ADI-41472 Heavy chain variable region

DITNYAQKFQG RVTIMADKSTSTAYMELSSLRSEDTAIYYC ARETSNFYFYYNAMDV (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 755 1510 QPVLTQPPSASGSPGQSVTISC TGTSSDVGGDNYVS WYQQHPGKAPKLLIY EVSKR ADI-41472 Light chain variable region

PS GVPDRFSGSRSGHTASLTVSGLQAEDEADYYC SSYAGRNNLGV FGGGTKLTVL (“LC”) amino acid sequence

Ab 756 1511 QVQLVQSGPGLVKPSQTLSLTCAISG DSVSSNSAAWS WIRQSPSRGLEWLG RTYYR ADI-41473 Heavy chain variable region

SKWYYDHAVSVEG RITINADTSKNHFSLQLNSVTPEDTAVYYC ARDPDSGNYFHYY (“HC”) amino acid sequence

GMDV WGQGTTVTVSS

Ab 756 1512 ETTLTQSPATLSLSPGERATLSC RTSQSVSSYLA WYQQKPGQAPRLLIY DASRRAT GI ADI-41473 Light chain variable region

PARFSGSGSGTHFTLTITSLEPEDFAVYYC QQRSKWPPYS FGQGTKVDIK (“LC”) amino acid sequence

Ab 757 1513 QVQLVQSGAEVKRPGASVKVSCKISG YTFTSHYIH WLRQAPGQGLEWMG WINPN ADI-41474 Heavy chain variable region

TGDTKYEQKFQG RVTMTRDTSLSTAYMELRRLRSDDTAVYYC ARDSFYAANGYYFV (“HC”) amino acid sequence

WFDP WGQGALVTVSS

Ab 757 1514 DIQMTQSPTSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPRFLIY AASSLQS G ADI-41474 Light chain variable region

VPSRFRGSGSGTDFTLTISSLQPEDFATYYC QQSYSSPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 758 1515 QVQLQESGPGLVKPSQTLSLTCAISG DSVSSNSAAWN WIRQSPSRGLEWLG RTYYR ADI-41475 Heavy chain variable region

SKWWTDYAVSVKS RITINPDTSKNQFSLQLNSVTPEDTAVYYC ARDPDSGNYFHYY (“HC”) amino acid sequence

GMDV WGQGTTVTVSS

Ab 758 1516 ETTLTQSPATLSLSPGERATLSC RASQSASSYLA WYQQKPGQAPRLLIY DASKRAT GI ADI-41475 Light chain variable region

PARFSGSGSGTDFSLTISSLEPEDFAVYYC QLRSKWPPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 759 1517 EVQLLESGGGLVQPGGSLRLSCATSG FRFTRYWMH WVRQAPGKGLEWVA RINFD ADI-41476 Heavy chain variable region

GTTTNYADSVKG RFTVSRDNAKNTLYLQINSLRAEDTAVYFC ARDQTFLEWLPFES (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 759 1518 QTVVTQEPSFSVSPGGIVTLIC GLTSGSVSTSYYPS WYQQTPGQAPRTLIY NTKTRF ADI-41476 Light chain variable region

SGVPDRFSGSILGNKAALTITGAQADDESDYYC VLYMSGGMV FGGGTKLTVL (“LC”) amino acid sequence

Ab 760 1519 QVQLVQSGAEVKKPGASVRVSCKASG YPFISYYIH WVRQAPGQGLEWMG MINTN ADI-41477 Heavy chain variable region

GGSTHYAQKFQG RVTMTRDTSTTTIYMELSRLKSEDTAYYFC ARDNTETVLHGFWS (“HC”) amino acid sequence

GYGSYLDY WGQGTLVTVSS

Ab 760 1520 EIVLTQSPGTLSLSPGGRATLSC RASQSVTSSYLA WYQQRPGQAPRLLIY GASSRAA ADI-41477 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSAPLT FGGGTKLEIK (“LC”) amino acid sequence

Ab 761 1521 QVQLVQSGAEVKKPGESLKISCKGSG YSFISYWIG WVRQMPGKGLEWMG IIYPAD ADI-41479 Heavy chain variable region

SDTRYSPSFQG QVTISVDKSISTAYLQWSSLKASDTGMYYC VRYGVGGTAPRY WG (“HC”) amino acid sequence

QGTTVTVSS

Ab 761 1522 NFMLTQPHSVSESPGKTVTISC TGSSGSIASNYVH WYQQRPGSAPTTVIY EDNQRP ADI-41479 Light chain variable region

S GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDISNLWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 762 1523 EVQLLESGPGLVRPSGTLSLTCTVS GDSISGSNWWA WVRQPPGRRLEWIG EIYYRG ADI-41480 Heavy chain variable region

ATDYNSSLKS RVIISVDNSKNQFSLNLRSVTAADTAIYYC ARVEKFATSGYYISYFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 762 1524 DIRVTQSPSSLSASVGDRVTITC RASQSISTYLN WYQHNPGKAPKLLIY AASSLQS GV ADI-41480 Light chain variable region

PSRFSGSGSGTHFTLTISSLQPADFSTYYC QQSYSSPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 763 1525 QVQLVESGPGLVKPSETLSLACSVSG VSISTYYWT WIRQPPGKGLEWIG YISYSGST ADI-41481 Heavy chain variable region

NYNPSLKS RVTISADTSKNQFSLRLNSVTAADTAVYYC ARTYYDFWSTYYGEFDH W (“HC”) amino acid sequence

G HGTLVTVSS

Ab 763 1526 SYELTQPLSVSVALGQTARITC GGNNIESKNVH WYQQKPGQAPVVVMY RDTNRPS ADI-41481 Light chain variable region

GIPERFSGSNSGNTATLTISRAQAGDEADYYC QVWDSGTAGVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 764 1527 QVQLVQSGAEVKKPGSSVKVSCKASG GTFGSYTIN WVRQAPGQGLEWMG GIIPIF ADI-41482 Heavy chain variable region

GATNYAQNFQG RVSITADKSTATAYMDLISLRSEDTAVYYC ARLGRSSPLNSCTTTS (“HC”) amino acid sequence

CYFWGRGMDV WGQGTTVTVSS

Ab 764 1528 QSVLIQPASVSGSPGQSITISC TGTISDVGIYNYVS WYQQHPGKAPKLIIS DVSDRPS ADI-41482 Light chain variable region

GVSNRFSGSKSGITASLTITGLQAEDEADYYC SSYSSSSTLYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 765 1529 EVQLVESGPGLVKPSEALSLTCTVSG ASISSYYWT WIRQSPRKGLEWIG YIYHTGRTN ADI-41484 Heavy chain variable region

YNPSLKR RVTMSVDWSKNQFSLTLSSVTAADTAVYYC ARLKVVPAALESAILEHHFG (“HC”) amino acid sequence

LDV WGQGTTVTVSS

Ab 765 1530 DIVMTQTPSTLSASIGDRVTLTC RASQSINRWLA WYQQKPGKAPKLLIY KASTLES G ADI-41484 Light chain variable region

VPSRFSGSGSGTEFTLTISGLQPDDFATYYC QQYNNFPYT FGPGTKVDIK (“LC”) amino acid sequence

Ab 766 1531 EVQLLESGPGLVRPSETLSLTCTVSGG SLDSGPHYWN WIRQPPGKGLEWIG YIYYSV ADI-41485 Heavy chain variable region

STNYNPSLKS RVTISMDTSKNQFSLNLTSVTAADTAVYYC ASFQLIYGPQI WGQGKK (“HC”) amino acid sequence

VTVSS

Ab 766 1532 DIVLTQSPSSVSASVGDRVTITC RASQAISSWLI WSQHKPGKAPKVLIY AASSLQS GV ADI-41485 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQANNFPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 767 1533 QVQLQQWGAGLLKPSETLSLTCSVYG GSFSGYYWS WIRQPPGKGLEWIG EINHSG ADI-41486 Heavy chain variable region

STNYNPSLKS RITISVDTSKNQFSLKLNSVTAADTAVYYC ARGDYAFVTFDY WGQGT (“HC”) amino acid sequence

LVTVSS

Ab 767 1534 QSVLTQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY EVSNR ADI-41486 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSTPV FGGGTKLTVL (“LC”) amino acid sequence

Ab 768 1535 QVQLVESGGGLVKPGGSLRLSCAASG FTFSTYTMN WVRQAPGKGLEWVS SISGSS ADI-41487 Heavy chain variable region

AYIYYADSVKG RFTISRDNAKNSLFLQMNSLRAEDTAVYYC ARLQGLVLPAVMPSYY (“HC”) amino acid sequence

YYSGMDV WGQGTTVTVSS

Ab 768 1536 EIVMTQSPLSLPVTPGEPASISC RSSQSLLHSNGYNYLD WYLQKPGQSPQLLIY LASN ADI-41487 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPQA FGQGTKVEIK (“LC”) amino acid sequence

Ab 769 1537 EVQLVESGPGLVKPSETLSLTCTVSG GSINSDYWN WIRQTPGKGLEWIG YIFYSGNT ADI-41488 Heavy chain variable region

NYNPSLKS RVTISIDTSKKKFSLQVTSVTAADTAVYYC ARMGTLKFDFDN WGQGTL (“HC”) amino acid sequence

VTVSS

Ab 769 1538 QSALTQPRSVSGSPGQSVTIPC TGTSSDVGAYKYVS WYQQHPGKAPKLIIY DVTKRP ADI-41488 Light chain variable region

S GVPNRFSGSKSGNTASLTISGLQAEDEADYYC CSYAGTHTYWV FGGGTKVTVL (“LC”) amino acid sequence

Ab 770 1539 EVQLVESGGGVVQPGRSLRLSCAASG FNFHNYAFH WVRQAPGKGLDWVA VTSYD ADI-41489 Heavy chain variable region

GSSAFYADSVKG RFTISRDNSKKILYLQMTSLRAEDTALYYC ARGSSSWSGDYFDY W (“HC”) amino acid sequence

GQGILVTVSS

Ab 770 1540 DIVMTQSPVTLSVSPGERATLSC RASQSVGSNLA WYQQKHGQTPRLLIY DASTRAT ADI-41489 Light chain variable region

SIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNKWPSYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 771 1541 EVQLLESGGGLVQPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS YMSSD ADI-41491 Heavy chain variable region

RSAIYYSDSVKD RFTISRDNAKNSLYLQMHSLRAEDTAVYYC ARRYCSSTSCYRGLGY (“HC”) amino acid sequence

YYGMDV WGQGTTVTVSS

Ab 771 1542 SYELTQPPSVSVAPGQTARITC GGSNIGNKDVH WYQQKPGQAPVLVVY DDSDRPS ADI-41491 Light chain variable region

GIPERFAGSNSGNTATLTISRVEAGDEADYYC QVWHSAGDHVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 772 1543 QVQLVQSGAEVRKPGSSVKVSCKASG GTFNSFVIS WVRQAPGQGLEWMG RIIPIL ADI-41492 Heavy chain variable region

ATVDYAQKFQG RVTITADKSTTTAYMELSGLTSEDTAVYYC ARDPPRWDTTMADY (“HC”) amino acid sequence

YYQGMDV WGQGTTVTVSS

Ab 772 1544 DIRVTQSPASLSAFVGDRVTISC RASQSIGSFLN WYQQKPGKAPKLLIY AASSLQS GV ADI-41492 Light chain variable region

PSRFSGSGSGTDFTLAISSLQPEDFATYYC QQSYRSTPT FGGGTKVEIK (“LC”) amino acid sequence

Ab 773 1545 QVQLVQSGAEVKKPGESLKISCKGSG YSFTKYWIG WVRQLPGKGLEWMG IIYPGD ADI-41493 Heavy chain variable region

SETIYSPSFQG QVTISADKSVSTAYLQWSSLKASDTAMYYC ARQTFVFWGESHDAF (“HC”) amino acid sequence

DI WGQGTTVTVSS

Ab 773 1546 QPVLTQPPSASGSPGQSVTISC TGTSSDVGAHNYVS WYQQHPGKAPKLMIY EVSK ADI-41493 Light chain variable region

RPS GVPDRFSGSKSGNTASLTVSGLQAEDEADYYC SSYAGSNNWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 774 1547 EVQLVESGGGLVQPGRSLRLSCTTSG FTFGDYAVT WVRQAPGKGLEWIG IMKSKTY ADI-41494 Heavy chain variable region

RGTTDYAASLRG RFSISRDDSKSIAYLQMTSLKSEDTGVYYC VRGHDYGDPFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 774 1548 QSVLTQPASVSGSPGQSITISC TGGSSDVGYYNYVS WYQQHPGKAPKLLIY DVNNR ADI-41494 Light chain variable region

PS GVSDRFSGSKSGNTASLTISGLQPEDEADYYC SSYTRSRTWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 775 1549 QVQLVQSGGGLVEPGGSLRLSCAASG FTFSNTWMN WVRQAPGKGLTWVG RIKR ADI-41495 Heavy chain variable region

KTDFGTSDYAAPVKG RFTISRDDSKNMVFLQMNSLKIEDTGVYYC TTHPRPYLDTT (“HC”) amino acid sequence

AVVY WGQGTLVTVSS

Ab 775 1550 QPVLTQPHSVSESPGKTVTISC IGSSGSITSNYVQ WFQQRPGSAPTTVIY EDDQRPS ADI-41495 Light chain variable region

GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYHHTNPWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 776 1551 QVQLVQSGAEVKKPGASVKVSCKASG YTFTSDDIN WVRQATGQGLEWMG WMN ADI-41496 Heavy chain variable region

PNSGDTGYAQKFQG RVTMTRDTSISTAYMELSSLRSEDTAVYYC ARVRIQCSGGRC (“HC”) amino acid sequence

SYWFFDL WGRGTLVTVSS

Ab 776 1552 QSALTQPASVSGSPGQSITISC IGTSSDVGNYNLVS WYQHHPGKAPKVMIY EVNER ADI-41496 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC CSYAGRSTWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 777 1553 QVQLVESGGGVVQPGRSLRLSCAASG FTFSNHAMH WVRQAPGKGLEWLS FISYD ADI-41497 Heavy chain variable region

GGVNFYRDSVKG RFTISRDNSKNTLYLQMSSLRPEDTAVYYC ARDRVGRVVGASYY (“HC”) amino acid sequence

LDY WGRGALVTVSS

Ab 777 1554 QSVVTQPPSVSVAPGQTASITC GGKHIGSKSVH WYQQKPGQSPVLVVH DDSDRPS ADI-41497 Light chain variable region

GILERFSGSNSGNTATLTINRVEAGDEADYYC QVWDNASDHPYV FGPGTKVTVL (“LC”) amino acid sequence

Ab 778 1555 EVQLLESGGGLVKPGGSLRLSCAASG FIFSDYAMN WVRQTPGKGLEWVS SISDSSA ADI-41498 Heavy chain variable region

YKYYTGSVSG RFTISRDNAKNSLYLQMNDLRPEDTAVFYC ARGQWRCSGASCYSPF (“HC”) amino acid sequence

DS WGQGTLVTVSS

Ab 778 1556 SYELTQPPSVSVAPGQTARIPC GGNNIESKNVH WYQQKPGQAPVLVVY DDSDRPS ADI-41498 Light chain variable region

GIPERFSGSNSGSTATLTISRVEAGDEADYYC HVWHRSGDLREV FGSGTKVTVL (“LC”) amino acid sequence

Ab 779 1557 EVQLVESGGVVVQPGGSLRLSCAASG FSFDDYTMY WVRQAPEKGLEWIS LISWNG ADI-41499 Heavy chain variable region

GVTYYPDSVKG RFTVSRDNNKNSLYLQMDSLRPEDSAFYYC AKESLESSGHFLDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 779 1558 QPVLTQSRSVSGSPGQSVTISC IGTNSDVGGYHYVS WFQHHPGKAPKLMIY DVSRR ADI-41499 Light chain variable region

PS GVPARFSGSKSGNTASLSISGLRAEDEADYYC CSFAGTYTPYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 780 1559 QVQLVQSGAEVKKPGSSVKVSCKASG GIFSDFAIS WVRQAPGQGLEWMG GIITIIG ADI-41501 Heavy chain variable region

TPEYAQKFQG RVRITADESTTTVFMELSRLTSEDTAVYYC ARDSRYGSGWYWDH W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 780 1560 DIVMTQTPDSLAVSLGERATINC KSSQSVLYISNNKNYLA WYQQKPGQPPKLLIY W ADI-41501 Light chain variable region

ASTRDS GVPDRFSGSGSGTDFTLSISSLQPEDVAVYYC QQYYDTPRT FGQGTKLEIK (“LC”) amino acid sequence

Ab 781 1561 QVQLVQSGAEVKKPGSSVKVSCKASG GPFSSDAMS WVRQAPGQGLEWMG GIIPI ADI-41502 Heavy chain variable region

LGSATYAQKFKG RVTIAADESTSTSYMELSGLKYEDTAVYYC ARPFYDPLTGYFDTFN (“HC”) amino acid sequence

V WGQGTTVTVSS

Ab 781 1562 QSVLTQPRSVPGSPGQSVTISC TGTSGDVGGYNYVS WYQQHPGKAPKLVIY DVTK ADI-41502 Light chain variable region

RPS GVPDRFSGSKSGNRASLTISGLQAEDEADYYC CSYAGSQTGYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 782 1563 EVQLLESGGGLVQPGGSLRLSCAASG FTFSDFPLS WVRQAPGKGLVWVS AISSSGG ADI-41503 Heavy chain variable region

DTYYADSVKG RFTISRDSSKNALYLQMNSLRAEDTAVYYC AKGQELLRPYYYGMDV (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 782 1564 QSALIQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQHPGKAPKLMIF EVSNR ADI-41503 Light chain variable region

PS GVSHRFSGSKSGNTASLTISGLQAEDEADYYC SSCTSRFTYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 783 1565 EVQLLESGPGLLKTSETLSLTCTVSD GSISGYYWT WIRQPPGKGLECIG YISYSGSTNY ADI-41504 Heavy chain variable region

SPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC AKIGGYCNPTKCYGWFDP WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 783 1566 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIF GNTNR ADI-41504 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEAAYYCQ SYDSSLFYVV LGGGTKLTVL (“LC”) amino acid sequence

Ab 784 1567 QVQLQQSGAGLLKPSETLSLTYVVYG GSFSGYYWS WIRQPPGKGLEWVG DINHST ADI-41505 Heavy chain variable region

TTNYNPSLES RITISIDTSKNQFSLNLSSVTAADSAVYYCA RGPKECTSSSCDRFGVDY (“HC”) amino acid sequence

FYYGMDV WGRGTTVTVSS

Ab 784 1568 QSVLTQPPSVSGAPGQRVTISC TGSSANIGAGYDVH WYQQFPGTAPKLLIF GNSNR ADI-41505 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAGDEADYYC QSYDGTLGGWV FGGGTQLTVL (“LC”) amino acid sequence

Ab 785 1569 QVTLKESGPTLVKPTQTLRLTCTFSG FSLNVISGVG VGWIRQPPGKALEWLA LIYWD ADI-41507 Heavy chain variable region

DDKRYSPSLKS RLTIAKDTSKNQVVLTMTNMDPVDTATYYC AHKGGSIEAAVGFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 785 1570 QSVLTQPPSVSGAPGQRVIISC TGSSSNIGAGFAVH WYQQLPGTAPKLLIY ANTNRP ADI-41507 Light chain variable region

S GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDTSLSGFYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 786 1571 QVQLVQSGAEVRKPGASVKVSCKASG YGFRSYDLT WVRQAPGKGLEWVG WISAY ADI-41508 Heavy chain variable region

SGGTNYAQTLQG RVTMTTDTSTSTAYMELRSLGPDDTAVYYC ARAGLYGSGSPDG (“HC”) amino acid sequence

FDS WGQGTLVTVSS

Ab 786 1572 SYELTQPPSVSVSPGQTASITC SGDKLGDKYAS WYQQRPGQSPVLVIS QDTKRPS GI ADI-41508 Light chain variable region

PERFSGSTSGNTAILTISGTQAMDEADYYC LAWDSSTAWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 787 1573 QVQLVESGGGLVQPGGSLRLSCAASG FTFSDYAMS WVRQAPGKGLVWVS SISGS ADI-41515 Heavy chain variable region

GKFTYYEDSLRG RVTISRDNSKNTVYLHMNSLRTEDTALYYC ARLRIPVINEVDGAM (“HC”) amino acid sequence

DV WGQGTTVTVSS

Ab 787 1574 SYELTQLPSVSVSPGQTARITC SGDALPKKFAY WYQQKSGQAPVLVIY EDTGRPS GI ADI-41515 Light chain variable region

PERFSGSTSGTTATLTINGAQVEDEGDYYC YSADSSDNQGV FGGGTKVTVL (“LC”) amino acid sequence

Ab 788 1575 EVQLLESGPRLVKPSETLSLTCIVSG GFISYDYWS WIRQPAGKGLEWIG RIYAGGIPK ADI-41516 Heavy chain variable region

YNPSLKS RVIMSLDMSNNQFSLRLKSVTAADSAVYYC ARAEPCSGDCFLGENPFDS (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 788 1576 QSVLTQPPSASGTPGQRVTISC SGSSSSIGSNYVY WYQQLPGTAPKLLIH KDNERPS ADI-41516 Light chain variable region

GVPDRFSGSKSGTSASLAISGLRSEDEGDYSC AAWDDSLSGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 789 1577 QVQLVQSGGGLVQPGGSLRLACAASG FTLSGYAMN WVRQAPGKGLEWVS SISGS ADI-41517 Heavy chain variable region

GGSTYYADSVKG RFTTSRDNSKNTVFLHMNSLRAEDTAIYYC ATVPWETGPFDH W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 789 1578 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYAVH WYQQLPGTAPKLLIH GTTNR ADI-41517 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSRLSGYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 790 1579 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-41518 Heavy chain variable region

YINYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTALYYC ARDLGYCSDTSCTPGIG (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 790 1580 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-41518 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSGLSPWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 791 1581 QVQLVESGPGLVKPSETLSLTCNVSG GSIITSGSYWG WIRQPPGKGLTWIG SISYSG ADI-41519 Heavy chain variable region

TTYYNPSLRS RLTISLDTSRNHFSLQLTSVSAADTAVYYC ARAFYEVWTGSEIPGDFD (“HC”) amino acid sequence

R WGQGTLVTVSS

Ab 791 1582 EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLIY GASSRAI DI ADI-41519 Light chain variable region

PDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQFRRSPWT FGQGTKVDIK (“LC”) amino acid sequence

Ab 792 1583 EVQLLESGGGVVRPGGSLRLSCAASG FSFDDYGMT WVRQAPGKGLEWVS GINW ADI-41520 Heavy chain variable region

NGISTDYADSVKG RFTISRDNAKNSVYLQMNSLRAEDTALYYC ARIGGVVVIASTAY (“HC”) amino acid sequence

YYGMDV WGQGTTVTVSS

Ab 792 1584 DIQLTQSPSSLSAYVGDRVTITC RASQSIRNHLN WYQQKPGKAPQLLIY TASSLQD G ADI-41520 Light chain variable region

VPSRFSGSGSGTDFTLAISSLQPEDFATYYC QQSHSMPPT FGQGTRLEIK (“LC”) amino acid sequence

Ab 793 1585 EVQLVESGGGLVQPGRSLRLSCAASG FTFDDFAMD WVRQVPGKGLEWVS GISWN ADI-41521 Heavy chain variable region

GVSKDYAGSVKG RFTISRDNAKNSLYLQMNSLRAEDTALYFC AKARRDVYNWGDA (“HC”) amino acid sequence

FDI WGQGTMVTVSS

Ab 793 1586 DIRLTQSPGTLSLSPGERATLSC RASQPLNSNYLA WYRQKPGQAPRLLIF DASSRAT ADI-41521 Light chain variable region

GVPDRISGSGSGTDFTLTVSRLEPEDIAVYYC QQYASSPWT FGLGTKVEIK (“LC”) amino acid sequence

Ab 794 1587 QVQLVQSGAEVKKPGSSVKVSCKASG GTFNNFPIS WVRQAPGQGLEWMG GIIPM ADI-41522 Heavy chain variable region

FGRANYAQKFQG RVTITADESTTTVYMALRSLRSEDTAVYYC ARPDYDVLTGFEGA (“HC”) amino acid sequence

FDI WGQGTMVTVSS

Ab 794 1588 QSALTQPASVSGSPGQLITISC TGTSRDVGGYNYVS WYQQHPGKAPKLMIY DVTNR ADI-41522 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQSEDEADYYC SSYTSTTTWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 795 1589 QVQLVQSGAEVKKPGESLRISCKGSG DTFSNYWIG WVRQMPGKGLEWMG IIYPG ADI-41523 Heavy chain variable region

DSDTRYSPSFQ GQVTFSADKSISTAYLQWSSLKASDTAMYYC VRQVGGVVVTDTD (“HC”) amino acid sequence

NYYYGMDV WGQGTTVTVSS

Ab 795 1590 DIRLTQSPSSLSASVGDRVTITC RASQSIRSYLN WYQQKPGKAPKLLIY SASSLQS GVP ADI-41523 Light chain variable region

SRFSGSGSGTDFTLTISSLQPEDFATYYC QQSHSTPLT FGPGTKVDIK (“LC”) amino acid sequence

Ab 796 1591 EVQLVESGGGLVQPGRSLRLSCTGSG FTFGDYAIS WFRQAPGKGLEWVG FIRSKPY ADI-41524 Heavy chain variable region

GGTTEYAASVKG TFTISRDDSKSIAYLQMNSLKTGDTAVYFC TRGIWGITMIVPWSD (“HC”) amino acid sequence

P WGQGTLVTVSS

Ab 796 1592 DIVMTQTPLSLPVTPGEPASISC RSSQSLLHSNGFNYLA WYLQKPGQSPQLLIY LNSN ADI-41524 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPLT FGPGTKLEIK (“LC”) amino acid sequence

Ab 797 1593 QVQLVQSGAEMKKPGSSVKVSCKASG RTFKYFALN WMRRAPGHGLEWIG GDIPIS ADI-41525 Heavy chain variable region

GSTNYAQKFQG RVTITADESASTAYMEVSRLRSDDTAVYYC ASLHYDVSTGFSDAF (“HC”) amino acid sequence

DI WGQGTMVTVSS

Ab 797 1594 QSVLTQPASVSGSPGQSITISC TGTSSDVGAYNYVS WYQHHPGKAPKLMIF DVSNR ADI-41525 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYRSTFSYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 798 1595 QVQLVQSGAEVKKPGASVKVSCEASG YTFTDYYMH WVRQAPGQGLEWMG WIN ADI-41526 Heavy chain variable region

PNSGVTKIAQNFQG RVTMTRDTSITTAYMDLSRLRSDDTAVYYC ARVVDGDYDN (“HC”) amino acid sequence

WFDF WGQGTLVTVSS

Ab 798 1596 SYVLTQPPSASGTPGQRVTISC SGSTSNIGTNTVN WYQQPPGMAPKLLIY ANNQRP ADI-41526 Light chain variable region

S GVPDRFSGSKSGTSASLAISGLQSEDEADYHC AVWDDSLPGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 799 1597 EVQLLESGGGLVQPGGSLRLSCAASG FTFTSYWMS WVRQAPGQGLEWVA TIKQD ADI-41527 Heavy chain variable region

GSEKYYVDSVKG RFTISRDNAKNSLYLQMNSLGAEDTAVYYC ARDMYCSTTTCYFF (“HC”) amino acid sequence

ETYYYNGMDV WGQGTTVTVSS

Ab 799 1598 DIRLTQSPSSVSASVGDRVTITC RASQVTSTWLA WYQQNPGKAPKLLIY AASRLQS G ADI-41527 Light chain variable region

VPSRFSGSGSGTEFTLTISSLQPEDFATYYC QQANSFPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 800 1599 EVQLVESGGGVVQPGRSLRLSCAASG FTFSSYAMH WVRQAPGKGLEWVA VISFD ADI-41528 Heavy chain variable region

GSSDYYADSVKG RFTISRDSSKNTLYLRMNSLRAEDTAVYYC ARRAVEYSIYNNDAF (“HC”) amino acid sequence

DV WGQGTTVTVSS

Ab 800 1600 SYELTQPPSVSVSPGQTASITC SGDKLGNKFTF WYQQKSGQSPVLVIY QETKRPS GIP ADI-41528 Light chain variable region

ERFSGSNSGNTATLTISGTQSMDEADYYC QAWDSSTAF FGGGTKLTVL (“LC”) amino acid sequence

Ab 801 1601 EVQLVQSGAEVRRPGSSVKVSCKASG GTLDTDSIS WVRQVPGQGLVWVG GVIPIL ADI-41529 Heavy chain variable region

GSVVYARKFQG RVTITADGSTSTAYMELRSLRSEDTAMYYC ASQFYDFRRGYFDAF (“HC”) amino acid sequence

DI WGQGTTVTVSS

Ab 801 1602 ETTLTQSPGILSLSPGERATLSC RATQTVISNYIN WYQQKPGQAPRLLIY GASSRAT GI ADI-41529 Light chain variable region

PDRFSGSGSGTDFTLTISRLEPEDFAVYYC QRYDSSPPGFT FGPGTKVDIK (“LC”) amino acid sequence

Ab 802 1603 QVQLVESGAEVKKPGASVKVSCRASG YTFSAYDIN WVRQAPGQGLEWVG WMNP ADI-41530 Heavy chain variable region

NSGNTGYALRFQG RVTMTRDTSINTAYMELSSLRSDDTAVYYC AAQLWYPN WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 802 1604 SYELTQPPSVSVGLGQTASITC GGNNIGSKSVH WYQQKPGQAPTLVIY RDTNRPS GI ADI-41530 Light chain variable region

PERFSGSNSENTATLTISRAQAGDEADFYC QVSDNYSWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 803 1605 EVQLLESGGDLVQPGGSLRLSCAASG FTFFSYALN WVRRTPGKGLEWVS GISGSGG ADI-41531 Heavy chain variable region

STYYADSVKG RFTISRDNSKSTLYLQMNSLKVDDTAVYFC AKDFQHDYGDPYRSYYF (“HC”) amino acid sequence

DH WGQGTLVTVSS

Ab 803 1606 DIQLTQSPSSLAASVGDRVTITC QASRDIRKSLN WYQVKPGKAPKLLIS DASYLET GV ADI-41531 Light chain variable region

PPRFSGSGFGTH FTFTISSLQPEDIATYYC QQYDNLPPPT FGGGTKVDIK (“LC”) amino acid sequence

Ab 804 1607 QVQLVQSGAEVKKPGESLKISCKGSG YSFTSSWIG WVRQMPGKGLEWMG IIYPGD ADI-41532 Heavy chain variable region

SDTRYSPSIQG RVTISADKSITTAYLQWSSLKASDTATYYC AKFGGYADAYFYHGMD (“HC”) amino acid sequence

V WGQGTTVTVSS

Ab 804 1608 SYVLTQPPSASGTPGQRVTISC SGSSSNVGSNTVN WYQQLPGTAPKLLIH FNNQRP ADI-41532 Light chain variable region

S GVPDRFSGSKSGTSASLAISGLQSEDEADYYC AAWDDSLNTWV FGGGTKVTVL (“LC”) amino acid sequence

Ab 805 1609 QVQLVESGGGVVQPGRSLRLSCAASG FTFSSYAMH WVRQAPGKGLEWLA VISFD ADI-41533 Heavy chain variable region

GSSEFYGDSVRG RFTISRDNSKNTLYLRVNSLRAEDTALYYC ARRSLKYSMYNNDAF (“HC”) amino acid sequence

DV WGQGTTVTVSS

Ab 805 1610 QPVLTQPPSVSVSPGQTASITC SGDKLGNKFTF WYQQKSGQSPVLVIY QESQRPS GI ADI-41533 Light chain variable region

PERFSGSNSGNTATLTIRGAQAMDEADYYC QAWDSSTAF FGGGTKLTVL (“LC”) amino acid sequence

Ab 806 1611 QVQLVQSGGGVVQPGRSLRLSCAASG FTFSNYAMH WVRQAPGKGLEWVT LISYD ADI-41534 Heavy chain variable region

GSAQDYADSVKG RITISRDNSKNTLYLQMSSLRPEDTAVYYC ARYYCTNDVCSSSAL (“HC”) amino acid sequence

DI WGQGTTVTVSS

Ab 806 1612 SYELIQPPSVSVSPGQTASITC SGDKLGNKFTC WYQQKPGQSPVLVIY QDSKRPS GIP ADI-41534 Light chain variable region

ERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTVV FGGRTKLTVL (“LC”) amino acid sequence

Ab 807 1613 QVTLKESGPALVKPTQTLTLTCTFSG FSLSTSRMCVS WIRQSPGKALEWLA RIDWD ADI-41535 Heavy chain variable region

DDKFFSTSLKT RLTISKDTSRNQVVLTMTNMDPVDTATYYC ARTTVYASGGYYLYYF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 807 1614 DIQLTQSPSSLPASVGDRVTITC RASQRIASYLN WYQQKPGKAPKVLIY AASNLQS G ADI-41535 Light chain variable region

VPSRFSGSGSGTDFTLTINSLQPEDFATYYC QQSYTTPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 808 1615 EVQLVESGAGLLKPSETLSLTCVVYG GSFSGYYWS WIRQPPGKGLEWVG DINHSTT ADI-41536 Heavy chain variable region

TNYNPSLES RITISIDTSKNQFSLNLSSVTAADSAVYYC ARGPKECTSSSCDRFGVDYF (“HC”) amino acid sequence

YYGMDV WGRGTTVTVSS

Ab 808 1616 QSVLTQPPSVSGAPGQRVTISC TGSSANIGAGYDVH WYQQFPGTAPKLLIF GNSNR ADI-41536 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDGTLGGWV FGGGTQLTVL (“LC”) amino acid sequence

Ab 809 1617 EVQLLESGGGLVQPGGSLRLSCAASE FTFSRYPMS WVRQAPGKGLEWVS GISVSG ADI-41537 Heavy chain variable region

DSTYYADSVKG RLTISRDNSKNTLYLQMNSLRAEDTAVYYC AIDHYDTSGYYGMDV (“HC”) amino acid sequence

WGQGTTVTVSS

Ab 809 1618 DIRLTQSPLSLPVTPGEPASISC RSSRSLLRSNGYNYLD WYLQKPGQSPQLLIY LGSNR ADI-41537 Light chain variable region

AS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQSSYT FGQGTKLEIK (“LC”) amino acid sequence

Ab 810 1619 EVQLVESGGGLVKPGGSLRLSCAASG FTLSTYGVN WVRQAPGKGLEWVS SISSSGN ADI-41538 Heavy chain variable region

NIHYADSVKG RFTVFRDNAKHSMYLQMNSLRAEDTAVYYC ARSLDYSNYYYYYGLD (“HC”) amino acid sequence

V WGQGTTVTVSS

Ab 810 1620 EIVLTQSPDSLAVSLGERATINC KSSQSIFYSSNNMNYLA WYQQKAGQPPKLLIY WA ADI-41538 Light chain variable region

STRES GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC HQYYSIPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 811 1621 QVQLVESGAEVKKPGASVKVSCKASG YNFIDYGIS WVRQAPGQGLEWVG WISAY ADI-41539 Heavy chain variable region

NGNTNYAQKLQG RVTMTTDTSTNTAYMELRSLRSDDTALYYC ARDSSSLHPTYYYY (“HC”) amino acid sequence

YPMDV WGQGTTVTVSS

Ab 811 1622 DIVMTQSPATLSVSPGERATLSC RASQSVSSRLA WYQQKPGQAPRLLIY GASTRAT ADI-41539 Light chain variable region

DVPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPPER TFGQGTKVEIK (“LC”) amino acid sequence

Ab 812 1623 QVQLQQWGAGLLKPSETLSLTCGVYG GSFTGYQWS WIRQSPGKGLEWIG DIDHG ADI-41540 Heavy chain variable region

GNTNYRPSLKS RIITSVNMSKKEFSLKLASVTAADTAVYYC ARGVGFLEFSGGPTGRR (“HC”) amino acid sequence

RNWFDS WGQGTLVTVSS

Ab 812 1624 DIQLTQSPGTLSLSPGEGATLSC RASQSVGGSYLA WYQQRPGQAPRLLIY GASNRA ADI-41540 Light chain variable region

A DSPDRFSGSGSATDFTLTISRLEPEDFAVYYC QQYGSSPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 813 1625 QITLKESGPTLVKPTQTLTLTCTFSG FSLSSSGVGVG WIRQPPGKALEWLA LIYWDD ADI-41541 Heavy chain variable region

DKRYSPSLKS RLTITKDTSKNQVVLTMTNMDPVDTATYYC AHRGPYYYDMSGYYYE (“HC”) amino acid sequence

AFDI WGQGTTVTVSS

Ab 813 1626 SYELMQPPSVSVAPGQTARITC GGNNIGSKGVH WYQQKPGQAPVLVVY DDNDRP ADI-41541 Light chain variable region

S GIPERFSGSNSGNTATLTISRVEAGDEADYYC QVWDSSSDHHYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 814 1627 EVQLVESGVAVKKPGESLKISCKGSG YNFDSFWIG WVRQLPGKGLEWMG IIFPGDS ADI-41542 Heavy chain variable region

DTRYGPSFQG QVTISADKSINTAYLQWRSLKASDTAMYYC ARHGLGGYDNSGYNL (“HC”) amino acid sequence

WGHGTMVTVSS

Ab 814 1628 DIVMTQSPSSLSASVGDRVTITC QASHDISTSLN WYQQKPGKAPNLLIS DASTLER G ADI-41542 Light chain variable region

VPSRFSGGGSGTEFTFTISSLQPEDIATYYC QQFENLPIT FGQGTRLEIK (“LC”) amino acid sequence

Ab 815 1629 QVQLVQSGAEVKKPGASVRVSCKASG YTLTGYYIH WLRQAPGQGLEWVG RINPNT ADI-41543 Heavy chain variable region

GETSYSQKFQG RVIMTRDTSVSTAYVDLSRLRSRDTAVYFC ARSDVMITVTAEGDFS (“HC”) amino acid sequence

YYYYRFDV WGQGTTVTVSS

Ab 815 1630 DIVMTQTPLSLPVTPGEPASISC RSSQSLLHSNGHNYLD WYLQKPGQSPQLLIY LGSI ADI-41543 Light chain variable region

RAS GVSDRFSGSGSGTDFTLKISRVEAEDVGIYYC MQALQTPH FGGGTKVEIK (“LC”) amino acid sequence

Ab 816 1631 QVQLVQSGAEVKKPGESLKISCKGSG YSFTNYWIG WVRQMPGKGLEWMG IIFPA ADI-41544 Heavy chain variable region

DSDTRYSPSFQG QVTISADKSVSTAYLQWTSLKASDTAIYYC ARLGVAAAGGY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 816 1632 DIQVTQSPSSLSASVGDRVTITC QASQDISNYLN WYQQKPGKAPKLLIH DASTLET G ADI-41544 Light chain variable region

VPSRFSGRGSGTDFTFTISSLQPEDIATYYC QQYDNLPPT FGGGTKVEIK (“LC”) amino acid sequence

Ab 817 1633 QVQLVESGPGLVKPSETLSLTCTVSG GSISRYYWS WIRQSPGKGLEWIG YIYHSVITN ADI-41545 Heavy chain variable region

YNPSLKS RVTISIDMSKNQFSLKLSSVTAADTAVYYC ASRPLINGYGPDNYFDY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 817 1634 SYVLTQPPSVSVAPGQTARITC GGNNIGSKSVH WYQRKPGQAPVLVVY DDSDRPS ADI-41545 Light chain variable region

GIPERFSGSNSGNTATLTIIRVEAGDEADYYC QVWDNSSDHPV FGGGTKLTVL (“LC”) amino acid sequence

Ab 818 1635 QVQLVQSGAEVKKPGESLKISCKGSG YSFTNYWIG WVRQMPGKGLEWMG IIFSAD ADI-41546 Heavy chain variable region

SDTRYSPSFQG QVTISADKSISTAYLQWSSLKASDTAMYYC ARQWGITGDAFDI WG (“HC”) amino acid sequence

QGTMVTVSS

Ab 818 1636 DIQVTQSPSFLSASVGDRVTITC RASQGISGYLA WYQQKPGKAPKLLIY AASTLQS G ADI-41546 Light chain variable region

VPSRFSGSGSGTEFTLTISSLQPEDFATYYC QQLNSYPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 819 1637 QVQLVQSGAEVKKPGSSVKVSCKASG GSFSSNTIN WVRQAPGQGLEWMG GIIPVF ADI-41547 Heavy chain variable region

ETPNYAQKFQG RVSFTADESTRTAYMELSSLRSEDTAVYFC ARQGMSYYDTNGNY (“HC”) amino acid sequence

YVGWFDT WGQGTLVTVSS

Ab 819 1638 EIVLTQSPGTLSLSPGERATLSC RASQSLNNNYLA WYQRKPGQAPRLLIY GAGAFSR ADI-41547 Light chain variable region

AT GIPDRFSGSGSGTDFTLTISRLEPEDFALYYC QQYGSSPLT FGQGTRLEIK (“LC”) amino acid sequence

Ab 820 1639 QVQLQQWGPGLVKPSETLSLTCTVSG ASITSHYWS WLRQPAGKGLEWIGR FYPSG ADI-41548 Heavy chain variable region

TTEKTPSLKS RVTLSVDTSKNHFSLKLTSVTAADTAVYYC ARDSYDDIAGSYEYYFAD (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 820 1640 EIVLTQSPATLSVSPGERATLSC RASQSVSSNLA WYQQKPGQAPRLLIY DISTRAT GV ADI-41548 Light chain variable region

PARFSGSGSGTEFTLTITSLQSEDFTVYYC QQYNNWPPT FGQGTKLEIK (“LC”) amino acid sequence

Ab 821 1641 EVQLLESGGGVVQPGGSLRLSCAASG FTFSGYGMH WVRQAPGKGLEWVA FIQYN ADI-41549 Heavy chain variable region

GSNKYYADSVKG RFTISRDNSKNTLYVQLNSLRAEDTAVYYC ATDILVVPAATPLISY (“HC”) amino acid sequence

YFGMD VWGQGTTVTVSS

Ab 821 1642 QSALTQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQYPGKAPKLMIY EVTNR ADI-41549 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC CSYTSTNTRV FGTGTKVTVL (“LC”) amino acid sequence

Ab 822 1643 QVQLVQSGAEVKMPGASVRVSCKASG YTLGSHGIT WVRQAPGQGLEWMG WISA ADI-41550 Heavy chain variable region

NNFNTHYAQKFQG RVTMTTDTSTSTAYMELRSLRSDDTAVYYC AREVMGHMVET (“HC”) amino acid sequence

ISFDY WGQGTLVTVSS

Ab 822 1644 QPVLTQPPSVSVAPGQTARITC GGNNIGSESVH WYQQKPGQAPVLVVH DDSDRP ADI-41550 Light chain variable region

S GIPERFSGSNSGNTATLTISRVEAGDEADYYC QVWDFTPDHPV FGGGTKVTVL (“LC”) amino acid sequence

Ab 823 1645 QVQLQESGGGVVQPGGSLRLSCAASG FTFSRHWMH WVRQVPGKGLVWVS RINS ADI-41551 Heavy chain variable region

DESTIDYADSVKG RFTISRDNAKNTLYLQMNSLRAEDTAVYYC VRDMVAVPGTTG (“HC”) amino acid sequence

GDY WGQGTLVTVSS

Ab 823 1646 SYELTQPPSVSVSPGQTADITC SGDKLGDKYAC WYQQRAGQSPILVLY QDTRRPS GI ADI-41551 Light chain variable region

PERFSGSNSGDTATLTISGTQAMDEADYYC QAWDSSTAWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 824 1647 QVQLVQSGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSS ADI-43643 Heavy chain variable region

SYIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARVLSGYSYGYDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 824 1648 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-43643 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV FGTGTKVTVL (“LC”) amino acid sequence

Ab 825 1649 EVQLVESGGGLVQPGGSLRLSCAASG FTFSSYAMS WVRQAPGKGLEWVS AISGSG ADI-43644 Heavy chain variable region

GSTYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKDFTVVHPLQQLTYY (“HC”) amino acid sequence

YFDY WGQGTLVTVSS

Ab 825 1650 DIVLTQSPATLSLSPGERATLSC RASQSVSSYLA WYQQKPGQAPRLLIY DASNRAT GI ADI-43644 Light chain variable region

PARFSGSGSGTDFTLTISSLEPEDFAVYYC QQRSNWPPGFT FGGGTKVEIK (“LC”) amino acid sequence

Ab 826 1651 QVQLVQSGAEVKKPGSSVKVSCKASGG TFSSYAIS WVRQAPGQGLEWMG GIIPIF ADI-43645 Heavy chain variable region

GTANYAQKFQG RVTITADESTSTAYMELSSLRSEDTAVYYC ARGWRGGGMTGSYY (“HC”) amino acid sequence

YYGMDV WGQGTTVTVSS

Ab 826 1652 DIQVTQTPSTLSASVGDRVTITC RASQSISSWLA WYQQKPGKAPKLLIY KASSLES GV ADI-43645 Light chain variable region

PSRFSGSGSGTEFTLTISSLQPDDFATYYC QQHRGT FGQGTKVDIK (“LC”) amino acid sequence

Ab 827 1653 EMQLMQSGGVVVQPGGSLRLSCAASG FTFDDYAMH WVRQAPGKGLEWVS LIS ADI-43646 Heavy chain variable region

WDGGSTYYADSVKG RFTISRDNSKNSLYLQMNSLRAEDTALYYC AKDFDPLVVPAA (“HC”) amino acid sequence

MCFDY WGQGTLVTVSS

Ab 827 1654 QSVLIQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY DVSNR ADI-43646 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSTLYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 828 1655 EVQLVESGGGLVQLGGPLRLSCAASG FTFSSYAMS WVRQAPGKGLEWVS AISGSG ADI-43647 Heavy chain variable region

GSTYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKGFERDYADAFDI W (“HC”) amino acid sequence

GQGTTVTVSS

Ab 828 1656 DIRMTQSPSSVSASVGDRVTITC RASQGISSWLA WYQQKPGKAPKLLIY AASSLQS G ADI-43647 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQANSFPIT FGQGTRLEIK (“LC”) amino acid sequence

Ab 829 1657 EVQLVQSGAEVKKPGASVKVSCKASG YTFTSYDIN WVRQATGQGLEWMG WMN ADI-43648 Heavy chain variable region

PNSGNTGYAQKFQG RVTMTRNTSISTAYMELSSLRSEDTAVYYC ATRPAALDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 829 1658 QPVLIQPLSVSVALGQTARITC GGNNIGSKNVH WYQQKPGQAPVLIIY RDSNRPS G ADI-43648 Light chain variable region

IPERFSGSNSGNTATLTISRAQAGDEADYYC QVWDSSTWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 830 1659 QVQLVQSGGGLVKPGGSLRLSCAASG FTFRDFYMS WIRQAPGKGLEWVS NISPSS ADI-36673 Heavy chain variable region

TYTNYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC VKSEGYSSGWYDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 830 1660 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVN WYHQLPGAAPKLLIY TNSNR ADI-36673 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 831 1661 EVQLVESGGGLVQPGGSLRLSCAASG FTFNRFAMS WVRQAPGKGLEWVS GISGS ADI-36675 Heavy chain variable region

GGSTLYADSVKG RFTISRDNSKNTLYLQINSLRVEDTAVYYC ASRSSYDDVWNGYVD (“HC”) amino acid sequence

WDWGFDFYYYGMDV WGQGTTVTVSS

Ab 831 1662 QAVVTQEPSMSAAPGQKVTISC SGGDSNIRNNYVF WYQQLPGTAPKLLIY DNTKR ADI-36675 Light chain variable region

PS GIPGRFSGSKSGASATLDITGLQTGDEADYYC GTWDSSLSALV FGGGTQLTVL (“LC”) amino acid sequence

Ab 832 1663 EVQLLESGGGVVQPGRSLRLSCAASG FSFRNYDMH WVRQAPGKGLEWVA IISYDG ADI-36676 Heavy chain variable region

SNKYADSVKG RFTISRDTSKNTLYLQMNSLRVEDTAVYYC ARADSSGYYKGSEYFQH (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 832 1664 SYELTQLPSVSVAPGQTARITC GGNNIGTKSVQ WYQHKPGQAPVLVVY DDSDRPS ADI-36676 Light chain variable region

DIPERFSGSNSGNTATLTISRVEAGDEADYYC QVWDSSSDHYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 833 1665 EVQLVQSGGGLVQPGGSLRVSCAASG LTVSTNYMS WVRQLPGKGLEWVS VIYSG ADI-36678 Heavy chain variable region

GNTYYADSVKG RFTISRDNSKNIVYLEMNSLRIEDTAVYYC ARAHLNNWFVSVTDT (“HC”) amino acid sequence

KDYYFDY WGQGTLVTVSS

Ab 833 1666 SYELTQPPSVSVLPGQTASITC SGDKLGDKYAS WYQQKPGQSPILVVF QDDKRPS GI ADI-36678 Light chain variable region

PERFSGSNSGNTATLTISGTQATDEADYYC QACDRNTGV FGTGTKLTVL (“LC”) amino acid sequence

Ab 834 1667 EVQLLESGGGLVQPGGSLRLSCAASG FTFSPYSMN WVRQAPGKGLEWVS YISRSG ADI-41552 Heavy chain variable region

SFKYYADSVKG RFTISRDDAKNSLYLHMNSLRDDDTAVYYC VSYCSSATCHQRFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 834 1668 EIVLTQSPATLSLSPGERATLSC RASQSVNSYLA WYQQKPGQAPRLLIY DASNRAT GI ADI-41552 Light chain variable region

PARFSGSGSGTDFTLTISSLEPEDFAVYYC QERNSWPKLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 835 1669 EVQLVESETEVKKPGASVKVSCKASG YTFTKYGIS WVRQAPGQGLEWMG WISAYN ADI-41553 Heavy chain variable region

GNTMYPHKLLG RVTMTTDTSTSTAYMELRSLRSDDTAVYYC ARDQTYYDFWSGYY (“HC”) amino acid sequence

TY WGQGTLVTVSS

Ab 835 1670 DIVMTQTPSTLSASVGDRVTITC RASQSISSWLA WYQQKPGKAPKLLIY KASSLES G ADI-41553 Light chain variable region

FTLTISSLQPDDSATYYC QQYNSYSRT FGQGTKVEIK (“LC”) amino acid sequence

Ab 836 1671 EVQLVESGGGLVQPGGSLRLSCAASG FTFSSYPMN WVRQGPGKGLEWVS SISSSG ADI-41554 Heavy chain variable region

ASPYYADSVKG RFTISRDNSKNTLYLQMNSLRADDTAVYYC AREDYYYYYMDV WG (“HC”) amino acid sequence

KGTTVTVSS

Ab 836 1672 ETTLTQSPSTLSASVGDRVTITC RASESISSWLA WYQQKPGKAPKLLIF KASTVQS GV ADI-41554 Light chain variable region

PSRFSGSGSGTEFTLTISSLQPDDFATYYC QQYNSYLLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 837 1673 EVQLVESGPGLVKPSQTLSLTCSVSG GSISSGIHYWS WIRQHPGKGLEWIG YIYYSGS ADI-41555 Heavy chain variable region

TYYNPSLES RITISVDTSKNQFSLKVSSVTAADTAVYYC ARVNRASRMTTFGVANERS (“HC”) amino acid sequence

IYYFMDV WGKGTTVTVSS

Ab 837 1674 ETTLTQSPATLSLSPGERATLSC RATQSVGNYLA WYQQKPGQAPRLLIH DASNRAT ADI-41555 Light chain variable region

GIPARFSGSGSGTDFTLTISSLEPEDFAVYYC QLRINWLFT FGPGTKVEIK (“LC”) amino acid sequence

Ab 838 1675 EVQLLESGGGLVKPGGSLRLSCAASG FSFSSYSMH WVRQAPGKGLEWVS SISSSSTY ADI-41556 Heavy chain variable region

IYYADSVKG RFTISRDNAKTSLFLQMNSLRAEDTAVYYC ARDPYSSGWYWD WGQG (“HC”) amino acid sequence

TTVTVSS

Ab 838 1676 EIVMTQSPATLSVSPGERATLSC RASQSVSGNLA WYQQKPGQAPRLLIY GASTRAT ADI-41556 Light chain variable region

GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC HQYNNRPAT FGQGTKVDIK (“LC”) amino acid sequence

Ab 839 1677 EVQLLESGPGLVKPSETLSLTCNVSG GSISSYYWS WIRQSPGKGLEWIG HIYDTGYT ADI-41557 Heavy chain variable region

NYNPSLKS RVTMSVDTSKNRFSLKLDSVTAADTAVYYC ARGRGWRNLYNWFDP W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 839 1678 DIVMTQSPATLSVSPGERATLSC RTSQSFSSMLA WYQQKPGQAPRLLIY GASTRAT ADI-41557 Light chain variable region

GIPARFSGSGSATEFTLTISNLQSEDVAVYYC QQYNSWPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 840 1679 EVQLLESGGGLVKPGGSLRLSCEVSG FPFSDYYVS WIRQAPGKGLEWLS YSSRGGIY ADI-41558 Heavy chain variable region

TNYADSVKG RFTISRDNDKNSLFLQMNSLRAEDTAVYYC ARDRSDIWSGRVGFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 840 1680 DIVMTQSPATLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLIY GASSRAT ADI-41558 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYNKSPPGYI FGPGTKVDIK (“LC”) amino acid sequence

Ab 841 1681 QVQLVQSGPTLVKPTQTLTLTCSFSG FSLTNTGVGVG WIRQPPGKALEWLA LIYWD ADI-41561 Heavy chain variable region

DDKRYRPSLKS RLTITKDTSKSQVVLTMTNMDPLDTATYYC AHRRSAYDPIYFDY W (“HC”) amino acid sequence

GQGALVTVSS

Ab 841 1682 DIRVTQSPSSVSASVGDRVTITC RASRSINNWLA WYQQKPGKAPKLLIY AASSLQS G ADI-41561 Light chain variable region

VPSRFSGSGYGTDFTLTISSLQPEDFATYYC QQAHSFPSIT FGQGTRLEIK (“LC”) amino acid sequence

Ab 842 1683 QVQLVQSGAEVKKPGASVRVSCKTSG YAFSKYGIS WVRQAPGQGLEWIG WISAYN ADI-41562 Heavy chain variable region

ENTHFSHKFLG RVTMTTDTSTGIAYMDLRSLKSDDTAVYYC ARDWYSLGSDWYFG (“HC”) amino acid sequence

PMFDY WGQGTLVTVSS

Ab 842 1684 EIVLTQSPDTLSVSPGERATLSC RASQSVTTNLA WYQQKPGHAPRLLIY GASTRAT GI ADI-41562 Light chain variable region

PARFSGSGSGTEFTLTISSLQSEDFAIYYC QQYTNWPRT FGQGTKVEIK (“LC”) amino acid sequence

Ab 843 1685 QVQLVESGPGLVKPSETLSLTCTVSD DSITNNFWT WIRQPPGKGLEWIG YIYYSGST ADI-41563 Heavy chain variable region

NYNPSLKS RITMSVDLSKNQFSLKLSSVTAADTAVYYC ARLTSGGVDY WGQGTLVT (“HC”) amino acid sequence

VSS

Ab 843 1686 QSVLTQPPSLSGAPGQRVTISC TGSSSNIGADYHVH WYQQLPGTAPKLLIY QNTNR ADI-41563 Light chain variable region

PS GVPDRFSASKSGTSVSLAITGLQAEDEADYYC QSYDSSLSAWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 844 1687 QVQLVQSGAEVKKPGSSVKVSCKAFG GTLRRYALS WVRQAPGQGLEWMG GIIPV ADI-41564 Heavy chain variable region

FGTRRYAQKFQG RITITADGSTSTASMEVSSLRFEDTAIYYC ATVYFDFVSGPPPTYY (“HC”) amino acid sequence

YYYMDV WGKGTTVTVSS

Ab 844 1688 DIVMTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLIY GASSRAT ADI-41564 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYDSSLRVLT FGGGTKVDIK (“LC”) amino acid sequence

Ab 845 1689 QVQLQQWGAGLLKPSETLSLTCEVYG GSFSGYYWT WFRQPPGEGLEWIG EINHSG ADI-41567 Heavy chain variable region

GTNYNPSLKS RVTMSVDASINQFSLQLSSVTAADTSVYYC ARGHYYNTNDFYGLFD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 845 1690 DIRLTQSPSFLSASVGDRVTITC RASQGISTYLA WYQQKPGKAPKLLLY AASTLHS GV ADI-41567 Light chain variable region

PSRFSGSGSGTEFTLTISSLQPEDFATYYC QQLNRYPPST FGPGTKLEIK (“LC”) amino acid sequence

Ab 846 1691 QVQLQQWGARLLKPSETLSLTCAVYG GSFSGYYWS WIRQSPGKGLEWIG EINHSG ADI-41568 Heavy chain variable region

STNYNPSLKS RVTISRDTSKKQFSLKVSSVTAADTAVYYC ARDPPIRCNGDSCKSDQY (“HC”) amino acid sequence

RYGMDV WGQGTTVTVSS

Ab 846 1692 QPGLTQPPSVSVSPGQTARITC SGDALPKQYAY WYQQKPGQAPVLVIH KDNERPS ADI-41568 Light chain variable region

GIPERFSGSSSGTTVTLTISGVQAEDEADYYC QSADTSGSYRL FGGGTKLTVL (“LC”) amino acid sequence

Ab 847 1693 EVQLLESGAEVKKPGSSVKVSCKASG GTFSTYAIS WVRQAPGQGLEWMG GIIPVLG ADI-41569 Heavy chain variable region

TTKYAQKFQD RVTITADESTSTAYMDLSGLRSDDTAVYYC ARGVWGDCGRASCLF (“HC”) amino acid sequence

DWYFDL WGRGTLVTVSS

Ab 847 1694 EIVMTQSPATLSVSPGERVTLSC SASQTVSSNLA WYQQKPGQAPRLLIY GASIRAT DI ADI-41569 Light chain variable region

PARFSGSGSRTEFTLTISSLQSEDFAVYYC QQYNNRPPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 848 1695 QVQLVQSGAEVKKPGSSVKVSCMASG GTFSNSAIN WVRQAPGQGLEWMG GTIPI ADI-41570 Heavy chain variable region

FGAANYAQRFQA RVTITADKSTSTAYMELTSLRSDDTAVYYC VRTPHRSSDHIWGS (“HC”) amino acid sequence

YRYFDS WGQGTLVTVSS

Ab 848 1696 QSVVTQEPSVSAAPGQKITISC SGSTSNIGINYVS WYQQFPGTAPKLLIY DNDKRPS G ADI-41570 Light chain variable region

IPDRFSGSKSGTSATLGITGLQAGDEADYYC GTWDSSLSAGHI FGGGTKVTVL (“LC”) amino acid sequence

Ab 849 1697 EVQLLESGGGLVKPGGSLRLSCEASG FPFNSYHMN WIRQSPGKGLEWVS YITGGSS ADI-41571 Heavy chain variable region

FSNYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARTTLDCTSTSCHYRFD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 849 1698 QSVLTQPPSVSGAPGQRITISC NGSNSNIGAGYDVH WYQQLPGKAPKLLIY SNNNR ADI-41571 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQGEDEADYYC QSHDTRLSGNVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 850 1699 QITLKESGPTLVKPTQTLTLTCTFSG FSLSTSGVGVA WIRQPPGKALEWLA LIYWDD ADI-41574 Heavy chain variable region

DKRYSPSLKS RLTITKDTSKNQVVLTMTNMDPVDTATYYC AHSSVYTTP FDYWGQ (“HC”) amino acid sequence

GSLVTVSS

Ab 850 1700 DIQLTQSPSTLSASVGDRVTITC RASQSISDWLA WYQQKPGKAPKLLIY KAFTLES GV ADI-41574 Light chain variable region

PSRFSGSGSGTEFTLTISSLQPDDFATYYC QQYTSYWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 851 1701 QVTLKESGPTLVKPTQTLTLSCSFSG FSLSAYAVGVG WIRQPPGKALEWLA LIYWDD ADI-41576 Heavy chain variable region

DKRYSPSLET RLTITKDTSKNQVVLTMTKMDPVDTATYYC VYSYNGYYEYMDV WG (“HC”) amino acid sequence

NGTTVTVSS

Ab 851 1702 DIVMTQSPATLSLSPGERATLSC RASQSVSNYLA WYQQKPGQAPRLLIS GASNRAT ADI-41576 Light chain variable region

GIPDRFSGSGSGTDFTLTITTPEPEDFAVYYC QQRNAWPRT FGQGTKVEIK (“LC”) amino acid sequence

Ab 852 1703 EVQLVESGGGVVQPGRSLRLSCAASG FTLSSYVMD WVRQAPGKGLEWVA VISYD ADI-41578 Heavy chain variable region

GSSKYYADSVKG RFTVSRDNSNNAMYLQMNSLRAEDTAVYYC ARDPYYDILTGYSY (“HC”) amino acid sequence

FDY WGHGTTVTVSS

Ab 852 1704 SYVLTQPPSVSGAPRQTATITC GGNNIGSKSVN WYQQKPGQAPVLVVY DDSARPS ADI-41578 Light chain variable region

GIPERFSGSNSGNTATLTVSSVEAGDEADYFC QVWDTSSAPYPWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 853 1705 QVQLVESGAEARKPGSSVKVSCKLSG GTFSTDPIS WVRQAPGQGLEWMG RIIPLLG ADI-41579 Heavy chain variable region

IANYAQKFQG RVTIIADKSTSTVYMELRNLRFEDTAVYFC ARRGDGYYGMDV WGQ (“HC”) amino acid sequence

GTTVTVSS

Ab 853 1706 QSVLTQPASVSGSPGQSITISC TGTSNDIGGYDYVS WYQQHPGKAPKLMIY DVHNR ADI-41579 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSFSDSGNLYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 854 1707 QVQLQQWGAGLLKPSETLSLTCAVYG GSFSGYYWS WIRQPPGKGLEWIG EMNHS ADI-41580 Heavy chain variable region

GGSNYNPSFKS RVTISVDTSKKYFSLNLSSVTAADTAIYYC ARTPFYYESTGYYYYYYG (“HC”) amino acid sequence

MDV WGQGTTVTVSS

Ab 854 1708 DIVMTQTPDSLAVSLGERATINC KSSQSVSHSSNNKNYLS WYQQKPGQPPKLLIY W ADI-41580 Light chain variable region

ASIRES EAPDRFTGSGSGTDFTLTISSLQAEDVAVYYC QQYYTAPIT FGQGTRLEIK (“LC”) amino acid sequence

Ab 855 1709 EVQLLESGSELKKPGASVKISCKTSG YTFTNYLMN WVRQAPGQGLEWMG WINTH ADI-41581 Heavy chain variable region

TGNPTYAQDFTG RFVFSLDTSVNTAYLQISSLKAEDTAIYYC ARDGLEAFSGYNGVD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 855 1710 DIVMTQTPLSLPVTPGEPASISC RSSPSLLHSNGYNYLD WYLQKPGQSPQLLIY LGST ADI-41581 Light chain variable region

RAS GVPDRFSGSGSGTDFTLRISRVEAEDVGVYYC MQALQIPLT FGQGTKLEIK (“LC”) amino acid sequence

Ab 856 1711 EVQLVESGPGLVKPSQTLSLTCTVSG GPISSGVYYWS WIRQHPGKGLESIG YIYYSGS ADI-41582 Heavy chain variable region

THYNPSLKT RVTISLDTSKNQFSLKLSSVTAADTAVYYC ARGCSGGSCYLYAFDI WG (“HC”) amino acid sequence

QGTTVTVSS

Ab 856 1712 QPVLTQPPSVSVAPGQTARITC GGNNIGTKSVH WYQQKPGQAPLLVVY DDSDRPS ADI-41582 Light chain variable region

GIPERFSGSNSGNTATLTISRVEAGDEADFYC QVWDYATDHVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 857 1713 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSRHTIT WVRQAPGQGLEWMG RIAPIV ADI-41583 Heavy chain variable region

GFANYAQKFQG RVTITADKSTSTAYMELRSLRSEDTAVYYC ARRSEDYYGLDV WG (“HC”) amino acid sequence

QGTTVTVSS

Ab 857 1714 DIVMTQSPSSLSASVGDRVTITC QASQDISNYLN WYQQKPGKAPKLLIY EASNLET G ADI-41583 Light chain variable region

VPSRFSGSGSGTDFTFTISSLQPEDIATYYC QQYDNL FGGGTKLEIK (“LC”) amino acid sequence

Ab 858 1715 QVQLVESGAEVKKPGASVKVSCKASG YTFTDYYIH WVRQAPGQGLEWVG RINPNS ADI-41584 Heavy chain variable region

GYINYAQKFQG RLTMTRDTSISTAYLELSSLRSDDTAVYYC TRLPLLEPLNFFDY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 858 1716 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKVLIY GNNN ADI-41584 Light chain variable region

RPS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSFDSSLSSSYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 859 1717 EVQLLESGGGLVKPGGSLRLSCAASG FTFADYYMS WIRQAPGKGLEWVS YISGGSS ADI-41585 Heavy chain variable region

FTNYADSVKG RFTISRDNAKNSLYLQMNSLRADDTAVYYC ARGISPALGGGEYFQD (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 859 1718 QPVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQHLPGTAPKLLIY GNSNR ADI-41585 Light chain variable region

PS GVPDRFSGSKSSTSASLAITGLQAEDEADYYC QSYDSSLGGYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 860 1719 QVQLQQWGAGLLKPSETLSLTCAVYG GSFSGYSWS WIRQPPGKGLEWIG DIDHD ADI-41586 Heavy chain variable region

GSTYYNSSLKS RVIMSIDTSKNQFSLKLSSVTAADTAVYYC ARVGGNSGY WGQGTL (“HC”) amino acid sequence

VTVSS

Ab 860 1720 DIVMTQTPLSLPVTPGEPASISC RSSQSLLHSNGFNYLD WYLQKPGQSPQLLIY LGSN ADI-41586 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTLT FGPGTKVEIK (“LC”) amino acid sequence

Ab 861 1721 QVQLVQSGAGLLKPSETLSLTCAVYG GSFSGYSWS WIRQPPGKGLEWIG EINYSVS ADI-41587 Heavy chain variable region

TSYNSSLKS RVSISVDTSKNQFSLKLTSVTAADTAVYYC ARVGGAVAD WGQGTLVT (“HC”) amino acid sequence

VSS

Ab 861 1722 EIVLTQSPLSLPVTPGEPASISC RSSQRLLHSNGYNYLD WYLQKPGQSPQLLIY LGSN ADI-41587 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQNLQTLT FGGGTKVDIK (“LC”) amino acid sequence

Ab 862 1723 QVQLVESGPTLVKPTQTLTLTCTFSG FSLSTNGVGVA WIRQPPGKALEWLA IIYWD ADI-41588 Heavy chain variable region

DDKRYSPSLKS RLTITKDTSKNQVVLTVTDMDPVDTATYYC AHTIGVPAATRFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 862 1724 SYELTQPPSVSVSPGQTASITC SGDKLGDKFAC WYQQKPGQSPVLVIY QDNKRPS GI ADI-41588 Light chain variable region

PERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTASYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 863 1725 EVQLLESGGGLVQPGGSLRLSCAASG FTFNFFALT WVRQAPGKGLEWVS AISGSGE ADI-41589 Heavy chain variable region

STYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKFARSGDYASFFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 863 1726 DIRVTQSPDSLAVSLGERATINC KSSQNVFYSSNNKNFLA WYQQKPGQPPKLLIY W ADI-41589 Light chain variable region

ASTRES GIPDRFSGSGSGTDFTLTISSLQAEDVAVYYC QQYYSTKFT FGPGTKVEIK (“LC”) amino acid sequence

Ab 864 1727 EVQLVQSGGGLVKPGGSLRLSCTASG FTFSDHYMS WIRQAPGKGLEWIS YISSTSSF ADI-41590 Heavy chain variable region

TNYANSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDRSILYSGYSLDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 864 1728 DIQMTQSPSSLSASVGDRVTISC RASQSILNYLN WYQHKPGKAPKLLIY AASSLQS G ADI-41590 Light chain variable region

VPSRFSGSGSGTDFTLTISGLQPEDFATYYC QQSDSTRT FGQGTKVEIK (“LC”) amino acid sequence

Ab 865 1729 QVTLKESGGGLVKPGGSLRLSCAASG FTFSDYYMS WIRQAPGKGLEWVS YISSSSSY ADI-41591 Heavy chain variable region

TNYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREAVAAAGTDYFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 865 1730 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQPPRTAPKLLIY GNSNR ADI-41591 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 866 1731 EVQLVESGSELKKPGASVKVSCKASG YTFRTYVMN WVRQAPGQGLEWMG WINT ADI-41592 Heavy chain variable region

NTGNPTYAQGFTG RFVFSLDTSVSTAYLQISSLKAEDTAVYYC ARESIDDYDSSGYGR (“HC”) amino acid sequence

TFDY WGQGTLVTVSS

Ab 866 1732 SYELTQPPSVSVSPGQTASIPC SGDKVGKTYVY WYQQTPGQSPGLVIY QDTKRPS GI ADI-41592 Light chain variable region

PERFSGSSSGNTATLTISGTQTMDEADYYC QAWDTSTASYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 867 1733 QVQLVQSGVEVKKPGESLKISCKGSG YSFTNYWIA WVRQMPGKGLEWMG IIYPG ADI-41593 Heavy chain variable region

DSDTRYSPSFQG QVTISADKSISTAYVQWSSLKASDTAIYYC ARGDILTNSGPDAFDI (“HC”) amino acid sequence

WGQGTMVTVSS

Ab 867 1734 DIQMTQSPSSFSASTGDRVTITC RASQAISSYLA WFQQKPGKAPKLLIY AASTLQS G ADI-41593 Light chain variable region

VPSRFSGSGSGTDFTLTISCLQSEDFATYYC QQYYSYPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 868 1735 EVQLVESGGGLVKPGGSLRLSCAASG FSFSSYYMN WVRQAPGKGLEWVS SISPSSS ADI-41594 Heavy chain variable region

YTNYADSVKG RFTISRDNAKDSLYLQMNSLRAEDTAVYYC ARDGLLGITIFGVVQDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 868 1736 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNTNR ADI-41594 Light chain variable region

PS GVPDRFSASKSGTSASLAITGLQAEDEADYYC QSYDSSLSVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 869 1737 QVQLVQSGGGVVQPGGSLRLSCAASG FTFSDYGMH WVRQAPGKGLEWVA VISD ADI-41595 Heavy chain variable region

GGSNQYSADSVRG RFTISRDNSKNTLYLQMNSLRPEDTAVYYC AKARIAARAIFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 869 1738 DIQLTQSPSSLSASVGERITITC QASRDVRIYLN WYQHKPGKAPKLLIY DASNLET GV ADI-41595 Light chain variable region

PSRYSGSGSGTDFTFTISSLQPEDIATYFC QQYDLLPPT FGVGTKVEIK (“LC”) amino acid sequence

Ab 870 1739 QVQLQQWGAGLLKPSETLSLTCAVYG DSFSGYFWT WIRQPPGKGLEWIG EINLSG ADI-41596 Heavy chain variable region

STNYNPSLKS RVTILVDTSKNQFSLKLSSVTAADTAVYYC ARGLHVSDDQDSSGYYF (“HC”) amino acid sequence

HPGSFDY WGQGTLVTVSS

Ab 870 1740 DIRMTQSPDSLAVSLGERATINC KSSQSVLYSSNNKNYLA WYQQKPGQPPKLLIN W ADI-41596 Light chain variable region

ASTRES GVPDRFSGSGSGTDFTLAISSLQAEDVAVYYC QQYYSTPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 871 1741 QVQLQESGPGLVKPSETLSLTCTVSG ASVSSNNYYWS WIRQPPGKGLEWIG YIYYS ADI-41597 Heavy chain variable region

GSTNYNASLKS RVTISVDTSKNQFSLKLSSVTAADTALYYC AGEHFGVASPFEAPFD (“HC”) amino acid sequence

Y WGQGTMVTVSS

Ab 871 1742 SSELSQPPSVSVAPGKTARITC GGNNIGIKSVH WYQQKPGQAPVLVIY SDSDRPS GI ADI-41597 Light chain variable region

PERFSGSNSGNTATLTITRVEAGDEADYYC QVWDSSSDHFV FGIGTKVTVL (“LC”) amino acid sequence

Ab 872 1743 EVQLVESGPGLVKPSETLSLTCTVSG GSITPYYWS WIRQPPGKGLEWIG NISYSGSTT ADI-41598 Heavy chain variable region

YNPSLKS RVTISVDRSKDQFSLRLRSVTAADTAVYYC ARVVTLVLGVSLNDAFDI WG (“HC”) amino acid sequence

QGTMVTVSS

Ab 872 1744 DIQMTQSPSSLSASVGDRVTITC RASQSISRYLN WYQHKPGKAPILLIY AATTLES GV ADI-41598 Light chain variable region

PPRFSGSGSGTDFSLTISSLQPEDFATYYC QQSYSVPLT FGGGTKLEIK (“LC”) amino acid sequence

Ab 873 1745 EVQLLESGGGLVQPGGSLRLSCAASG FIFSNYEMN WVRQAPGKGLEWIS HITPTGN ADI-41599 Heavy chain variable region

SIYYADSVKG RFTISRDNAKNAQYLQMHSLRPDDTAIYYC ARGEDPIAATGGFDS W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 873 1746 EIVLTQSPSSLSASVGDRVTIPR RSSQNVDKFLH WYQQRPGKAPKLLIY AAFSLQS GV ADI-41599 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPFT FGQGTKVEIK (“LC”) amino acid sequence

Ab 874 1747 EVQLLESGGNMVQPGKSLRLSCAASG FTFSNYGMH WVRQAPGKGLEWVA VISKD ADI-41600 Heavy chain variable region

GNNEHYADSVRA RFTVSRDNSKNTLFLQMNSLRPEDTAVYYC AIGGLSGSYFGEYF (“HC”) amino acid sequence

QH WGRGTLVTVSS

Ab 874 1748 DIQMTQSPSSMSASLGDRVTITC RASQGISTWLA WYQQKPGEAPKLLIY AAFGLQS ADI-41600 Light chain variable region

GVPSRFSGSGSGTDFTLTINNLQPEDFATYYC QQAISFPFT FGGGTKVEIK (“LC”) amino acid sequence

Ab 875 1749 EVQLLESGGGLVKPGGSLRLSCAGSG FRFSDYYMT WIRQAPGKGLEWVS YISSSSTY ADI-41601 Heavy chain variable region

TYYTDSVKG RFTVSRDNAKNSLYLQMNTLRAEDTAIYYC AISNRYDSRTFYYDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 875 1750 QSVLTQPPSVSGAPGQRVIISC TGSSSNIGAGYDVH WYQQFPGTAPKLLIY GNNNR ADI-41601 Light chain variable region

PS GVPERFSGSKSGTSASLAITGLQADDEADYYC QSYDSLSEVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 876 1751 EVQLQESGPGLVKPSETLSLTCTVSG GSLSGYYWS WIRQPPGKGLEWIG YIYHSGST ADI-41602 Heavy chain variable region

NYNPSLES RVTISVDTSKNQFSLKVNAVTAADTAVYYC AKVERLLRFDP WGQGTLV (“HC”) amino acid sequence

TVSS

Ab 876 1752 QSVLIQPASVSGSPGQSITISC IGSSSDVGGYNYVS WYQHYPGKAPKLMIY DVSNRP ADI-41602 Light chain variable region

S GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSTSYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 877 1753 EVQLVESGGGLVKPGRSLRLSCTTSG FTFGDYAMS WFRQAPGKGLEWVG FIRSKPY ADI-41603 Heavy chain variable region

GGATAYAASVRG RFTISNDDSKSIAYLQMESLKIEDTAVYYC ARDYDDFFFYDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 877 1754 DIRMTQSPATLSVSPGERATLSC RASENIYSNLA WYQQKPGQAPRLLIY GASTRAT G ADI-41603 Light chain variable region

LPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPA FGGGTKVEIK (“LC”) amino acid sequence

Ab 878 1755 QVTLKESGAEVKKPGASVKVSCKASG YTFTGYYMH WVRQAPGQGLEWMG RINP ADI-41604 Heavy chain variable region

NSGGTNYAQKFQG RVTMTRDTSISTAYMELSRLRSDDTAVYYC AREASRFGGFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 878 1756 DIVLTQSPSSLSASVGDRVTITC QASQDISNYLN WYQQKPGKAPKLLIY DASNLET G ADI-41604 Light chain variable region

VPSRFSGSGSGTDFTFTISSLQPEDIATYYC QQYDNLLGYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 879 1757 QVQLVESGPGLVKPSQTLSLTCSVSG GSISSDDHYWS WIRQHPGKGLEWIG YIYYS ADI-41605 Heavy chain variable region

GYTNYNPSLKS RVTISVDTSKNQFSLRLSSVTAADTAVYYC ARETDITIFGVVPVGYF (“HC”) amino acid sequence

DY WGQGTLVTVSS

Ab 879 1758 DIQVTQSPDSLAVSLGERATINC KSSQSILSSTNNKNFLA WYQQKPGQPPKLLLH W ADI-41605 Light chain variable region

ASTREF GVPDRFSGSGSGTEFTLTISSLQAEDVAVYYC QQYYTTPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 880 1759 EVQLLESGPGLVKPSETLSLTCTVSGG SVSSGGYYYT WIRQPPGKGLEWIG YAFYSG ADI-41606 Heavy chain variable region

DTNYNPSLKS RVTISVDTSKNQFSLKLTSVTAADTAVYYC ASTYTFGASGFDF WGQG (“HC”) amino acid sequence

TLVTVSS

Ab 880 1760 DIVMTQSPSFMSASVGDRVTITC RASQGISNWLL WYQQKPGKAPKLLIY AASSLQS ADI-41606 Light chain variable region

GVPSRFSGSRSGTDFTLTISSLQPEDFAIYYC QQANSFPLT FGQGTRLEIK (“LC”) amino acid sequence

Ab 881 1761 EVQLVESGPGLVKPSQTLSLTCTVSG GSINIGGYYWS WIRQHPEKGLEWIG YIYYSG ADI-41607 Heavy chain variable region

TTYYNPSLES RVTISIDTSKNQFSLNLSSVTAADTAVYYC ASVDQIGATRFDY WGQG (“HC”) amino acid sequence

TLVTVSS

Ab 881 1762 QPVLTQPRSVSGSPGQSVTLSC TGTSSDVGTYNYVS WYQHHPGKAPKLIIY DVNKR ADI-41607 Light chain variable region

PS GVPDRFSGSKSGNTASLTISGLQAEDEADYYC CSYAGSYTLNYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 882 1763 QVQLVQSGDEVKKPGESLKISCKGSE HTFTNYWIA WVRQMPGKGLECMG VIWPD ADI-41608 Heavy chain variable region

DSDTKYSPSFQG QVTISADKSINTAYLHLSSLRASDTAMYYC ATSKFRTGFDF WGQG (“HC”) amino acid sequence

TLVTVSS

Ab 882 1764 NFMLTQPHSVSESPGKTVIISC TRSSGNIASNYVQ WYQQRPGSSPTTVVY EDNQRP ADI-41608 Light chain variable region

SGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC QSYDSSNPWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 883 1765 QVQLVESGAEVKKPGASVKVSCKASG YSFTSYYMH WVRQAPGQGLEWMG VISTN ADI-41609 Heavy chain variable region

GGTASYSQNFRG RVILTRDTSTSTAYMELSSLTSEDTAVYYC VREGYCNGGSCSYFD (“HC”) amino acid sequence

S WGQGTLVTVSS

Ab 883 1766 QSVLTQPPSVSGAPGQRVSISC TGSSSNIGAGYDVH WYQQLPGTAPKVLIY GNNYR ADI-41609 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQTEDEADYYC QSYDSRLSVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 884 1767 EVQLLESGGGVVQPGRSLRLSCAASE LSFRNYGMH WVRQAPGKGLEWVA VISYD ADI-41610 Heavy chain variable region

GNDKYYADSVKG RFTISRDNSKKTLYLQMDSLRAEDTAVYYC AKEGAYCGGDCFSS (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 884 1768 GIQLTQSPSSLSASVGDRVTITC RASQSSSSYLN WYQQKPGKAPKLLIY AASSLQS GV ADI-41610 Light chain variable region

PSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYS FGGGTKVEIK (“LC”) amino acid sequence

Ab 885 1769 EVQLVESGGGLVKPGGSLRLSCAASG FTFSDYSMN WVRQAPGKGLEWVS STSSGS ADI-41611 Heavy chain variable region

TYIYYADSVKG RFTISRDNGKNSLYLQMNSLRAEDTAVYYC ARAFRLGYDALDI WG (“HC”) amino acid sequence

QGTMVTVSS

Ab 885 1770 DIRMTQSPSSLSASVGDRVTIIC RASQSISNYLN WYQQKPGKAPKLLIY VASNLQS G ADI-41611 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQTYSPPPT FGGGTKLEIK (“LC”) amino acid sequence

Ab 886 1771 EVQLQESGPGLVKPSGTLSLTCAVAG GFISSGNWWS WIRQPPGKGLEWIG EVYHS ADI-41626 Heavy chain variable region

GRTSYNPSLKS RVTISVDNSKNQFSLKMSSVTAADTAVYYC ARVESYSSSGYYIAYD (“HC”) amino acid sequence

N WGQGNLVTVSS

Ab 886 1772 DIVLTQSPSSLSASVGDRVTITC RASQSISRYLS WYQQKPGKAPKLLIY AAFSLQT GVP ADI-41626 Light chain variable region

SRFSGSGSGTDFTLTISSFQTEDSATYYC QQSYSAPVT FGGGTKVEIK (“LC”) amino acid sequence

Ab 887 1773 QVQLQQWGPGLVKPSETLSLSCAVSG GSLRGHFWS WIRQPPGKGLEWIG EINHG ADI-41644 Heavy chain variable region

GRTNFNPSLKS RLTISEDSSKNQFSLKLSSVTAADTAVYYC ARRWGYDSSGYYFFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 887 1774 EIQMTQSPATLSVSPGERATLSC RASQTLGFNLA WYQQKPGQSPRLLIY GASTRAT ADI-41644 Light chain variable region

GIPARFSGSGAGTEFTLTISSLQSEDFAVYFC QQYSNYYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 888 1775 EVQLVQSGAEVKKPGSSVKVSCKASG GTFSRNAIS WVRQAPGQGLEWMG GIIPIF ADI-41660 Heavy chain variable region

GAANYPQKFQG RVTITADKSTSTAYMELSSLRSEDTALYYC ARTMGEMTTTPVSIYY (“HC”) amino acid sequence

YGMDV WGQGTTVTVSS

Ab 888 1776 QSVLTQPPSVSAAPGQKVTISC SGSSSNIGINYVS WYQQLPGTAPKLLIY DNNKRPS ADI-41660 Light chain variable region

GIPDRFSGSKSGTSATLGITGLQTGDEADYYC GTWDSSLSAGYV FGSGTKLTVL (“LC”) amino acid sequence

Ab 889 1777 QVQLVQSGAEVKKAGESLKISCKGPR HSFTSYWIG WVRQMPGKGLEWMA SIYPG ADI-41662 Heavy chain variable region

DSDSRYSPSFEG QVTISADKSIDTAFLQWSSLKASDTAMYFC ARYVGAVPGGNWYF (“HC”) amino acid sequence

DL WGRGTLVTVSS

Ab 889 1778 SYELIQLPSVSVSPGQTARITC SGDALPKKYAY WYQQKSGQAPVLVIY DDNKRPS GI ADI-41662 Light chain variable region

PARFSGSSSGTMATLTISGAQVEDEGDYYC YSTDSTGDHRGV FGGGTKLTVL (“LC”) amino acid sequence

Ab 890 1779 EVQLVQSGDEVKKPGASVKVSCKASG YPFSTYGIS WVRQAPGQGLEWMG WIGVY ADI-41664 Heavy chain variable region

TGGTNYAQKFQG RVILTIDTSTSTAYMELRSLRSDDTAVYYC ARGTGSYMTATYFD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 890 1780 SYELTQPPSVSVAPGQTARITC GGNNIGSKAVH WYQQKPGQAPVLVVY DDYDRPS ADI-41664 Light chain variable region

GIPERFSGSNSGNTATLTISRVEAGDEADYYC QVWDSSSDYV FGTGTKLTVL (“LC”) amino acid sequence

Ab 891 1781 QVTLKESGPALVKPTQTLTLTCTFSG FSLSTSRMCVS WIRQPPGKALEWLA RIDWD ADI-41677 Heavy chain variable region

GDIYYSTSLRT RLTISKDTSKNQVVLTMTNMDPVDTATYYC ARTSIYATGGYYLYYSD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 891 1782 EIVMTQSPSSLSASVGDRVTITC RASQSIASYVN WFQQKPGKAPKLLIY AASNVHS G ADI-41677 Light chain variable region

VPSRFSGSGSGTGFTLTISSLQPEDSAIYYC QQSYTTPWT FGQGTKLEIK (“LC”) amino acid sequence

Ab 892 1783 EVQLVESGGGVVQPGGSLRLSCAASG FTFRTYGMH WVRQAPGKGLEWVA VISYD ADI-41678 Heavy chain variable region

GSNKYYADSLMG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKCFVPGSGGWYE (“HC”) amino acid sequence

YYFDY WGQGTLVTVSS

Ab 892 1784 QSVLTQPPSASGSPGQSVTISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY EVSKR ADI-41678 Light chain variable region

PS GVPDRFSGSKSGNTASLTVSGLQAEDEADYYC SSYAGINNSVL FGGGTKLTVL (“LC”) amino acid sequence

Ab 893 1785 QVQLVQSGAEVKKPGESLRISCKGSG YSFSSHWIG WVRQKPGKGLEWMG IIYPGD ADI-41690 Heavy chain variable region

SDTRYSPSFQG HVTISADKSISTAYLRWSSLKASDTAIYYC AKRMVGDYYGMNL WG (“HC”) amino acid sequence

QGTTVTVSS

Ab 893 1786 EIVMTQSPSSLSASVGDRVTITC QASQDISNRLN WYQQKPGKAPKLLIY DASNLET G ADI-41690 Light chain variable region

VPSRFSGSGSGTDFTFTISSLQPEDIATYFC QQYDYLLWFT FGPGTKVDIK (“LC”) amino acid sequence

Ab 894 1787 QVQLVQSGAEVKKPGESLKISCQASG YSFTTYWIG WVRQTPGKGLEWMG IIYPGD ADI-41701 Heavy chain variable region

SDTRYTPSFQG QVTISADKSISTAYLHWSSLKASDTAMYYC ARLSGGYTFGFDY WGL (“HC”) amino acid sequence

GTLVTVSS

Ab 894 1788 NFMLTQPHSVSESPGKTVTISC TRSSGNIARYYVQ WYQQRPGRAPTTVIY EDDQRP ADI-41701 Light chain variable region

S GVPDRFSGSIDRSSNSASLTISGLKTEDEADYYC QSYDASNYV FATGTKVTVL (“LC”) amino acid sequence

Ab 895 1789 EVQLLESGSGLVKPLQTLSLTCAVSG GSISSGGYSWS WIRQPPGKGLEWIG YIYPSGS ADI-41703 Heavy chain variable region

TYYNPSLKS RVTMSIDRSKNQFSLRLTSVTAADTAVYYC ARGDGNDFWSADSSHAF (“HC”) amino acid sequence

AI WGQGTMVTVSS

Ab 895 1790 EIVMTQSPGILSLSPGERATLSC RASQIVGNSYLA WYQQKPGQAPRLLIY GASSRAT ADI-41703 Light chain variable region

GIPERFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSSPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 896 1791 QVQLVESGGGVVQPGRSLRLSCAASG FTFSSYGMH WVRQAPGKGLEWVS VIWFD ADI-41720 Heavy chain variable region

GSKKYYEDSVKG RFTISRDNSKNTLYLEMNSLRAEDTAVYYC AREAPVRLGELSLYGY (“HC”) amino acid sequence

FDY WGQGTLVTVSS

Ab 896 1792 DIQMTQSPSTLSASVGDRVTITC RASQSFSSWLA WYQQKPGKAPKLLIY DASTLES G ADI-41720 Light chain variable region

VPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQYNSYSWT FGQGTKLEIK (“LC”) amino acid sequence

Ab 897 1793 QVQLQESGPGLVKPSQTLSLTCTVSG GSMISGDFYWS WIRQPPGKGLEWIG YIYYS ADI-41737 Heavy chain variable region

GTTYYSPSLKS RVSMSIDTSKSQFSLKLSSVTAADTAVYYC ARKYSYGEKAYHY WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 897 1794 EIVLTQSPGTLSLSPGERATLSC RASQTVGNNYLA WYQQKPGQAPRLLIY GASSRAT ADI-41737 Light chain variable region

GIPDRFSGSGSGTDFTLTISRLESEDFAVYHC HQYGTSPQT FGQGTKVEIK (“LC”) amino acid sequence

Ab 898 1795 EVQLVESGSGLVKPSQTLSLTCSVSG GSISSGGYSWS WIRQPPGKGLEWIG FIYNTG ADI-41743 Heavy chain variable region

STYSNPSLKS RLTLSVDRSNNRFSLKLNSVTAADTGVYFC ARSGNVRQCDATGHCST (“HC”) amino acid sequence

NYYFEY WGLGTLVTVSS

Ab 898 1796 EIVMTQSPATLSVSPGERATLSC RASQSVSSNLA WYQQKPGQAPRLLIY GASTRAT ADI-41743 Light chain variable region

GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQHDDWPPLT FGGGTKVEIK (“LC”) amino acid sequence

Ab 899 1797 EVQLLESGGGVVQPGRSLRLSCAASGL SFNSFGMH WVRQAPGKGLEWVA VIAYD ADI-41756 Heavy chain variable region

GSNKYYADSVKG RFSISRDNSKNTLYLQMDSLRAEDTAVYYC AKAEAPNFSWSGYL (“HC”) amino acid sequence

SAFDI WGQGTTVTVSS

Ab 899 1798 QPVLIQPASVSGSPGQSVIVSC TGTSDDVGDYNYVS WYQQHPGKAPKLLI FEVSD ADI-41756 Light chain variable region

RPS GVSTRFSGSKSGNTASLTISGLQTEDEADYYC SSYTSRNLYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 900 1799 EVQLVESGGGLVQPGRSLRLSCAASG FTFGDYAMH WVRQAPGKGLEWVS GITW ADI-41768 Heavy chain variable region

NSGRVVYADSVKG RFTISRDNAKNSLYLQINSLRAEDTALYYC VKGSCNGGICYSAD (“HC”) amino acid sequence

Y WGQGTLVTVSS

Ab 900 1800 NFMLTQPHSVSESPGKTVTISC TRSSGSIARNFVH WYQQRPGSSPTTVIY EDNQRPS ADI-41768 Light chain variable region

GVPGRFSGSIDSSSNSASLTISGLRSEDEADYYC QSYDSDNWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 901 1801 EVQLLESGGGLVEPGTSLRLSCEASG FTFSDYYMS WIRQAPGKGPEWVA DISSRGV ADI-41772 Heavy chain variable region

VTYYADSVKG RFTISRDNAKNSLYLQLNSLGAEDTAVYYC ARLREVTYIMPTIDYFDY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 901 1802 SYELTQPPSVSVSPGQTARITC SGDAFVKKYAY WYHQKSGQAPVVVIY EDTKRPS GI ADI-41772 Light chain variable region

PERFSGSSSGTTATLTISGAQVEDEGDYYC YSRDFSGDHGV FGGGTKLTVL (“LC”) amino acid sequence

Ab 902 1803 QVQLVESGGGQGQPGRSLRLSCAASG FTFDDYAMH WVRQVPGKGLEWVS GIN ADI-41778 Heavy chain variable region

WNSGYIGYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTALYYC AKANNPIDSSGY (“HC”) amino acid sequence

NRGFDT WGQGTLVTVSS

Ab 902 1804 QSALTQPRSVSGSPGQSVTISC TGTSSDVGGYNYVS WYQQHPGKAPKLMIY DVNK ADI-41778 Light chain variable region

RPS GVPDRFSGSKSDNTASLTISGLQAEDESDYFC CSYAGTYTWV FGGGTKVTVL (“LC”) amino acid sequence

Ab 903 1805 QVQLVQSGAEVRKPGASVKVSCKAFG YTFTNFAIS WVRQAPGQGLEWMG WIGP ADI-41781 Heavy chain variable region

YNGDTDYEQKFQG RVTMTADTSSSTVFMELRSLRFDDTAVYYC ARGKGSTIPLGYYI (“HC”) amino acid sequence

GMDV WGQGTTVTVSS

Ab 903 1806 ETTLTQSPSSLSASVGDRVTMTC RASQGISNYLA WYQQKPGKPPKLLIY LASSLQS G ADI-41781 Light chain variable region

VPSRFSGSGSGTDFTLTISSLQPEDVATYYC QKYNSAPLT FGGGTKLEIK (“LC”) amino acid sequence

Ab 904 1807 QVQLVQSGDEVKKPGASVKVSCKSSG YTFTHFGVS WVRQAPGQGLEWMG WISG ADI-41783 Heavy chain variable region

YNGNTNYAQKLQG RVTMTTDTSTTTAYMELTSLRSDDTAVYYC ARDSPAGTVTLD (“HC”) amino acid sequence

F WGQGTTVTVSS

Ab 904 1808 DIVMTQSPLSLPVTLGQPASISC RSSQSLVYSDGNTYLN WFQQRPGQSPRRLIY KVS ADI-41783 Light chain variable region

NRDS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MHGTHWPPEYT FGQGTKVE (“LC”) amino acid sequence

IK

Ab 905 1809 EVQLLESGGGVVQPGRSLRLSCAASG FTFSSSGMH WVRQAPGKGLEWVA IISSDG ADI-41787 Heavy chain variable region

SKHYYADSVKG RFTISRDNSKNTLYLEMNSLRAEDSAVYYC AREGVWSGFFVDTGT (“HC”) amino acid sequence

DFRHHGMDV WGQGTTVTVSS

Ab 905 1810 SYELTQPPSVSVSPGQTARITC SGDALPKKFAF WYQQKSGQAPLLVIHE DNKRPSGI ADI-41787 Light chain variable region

PERFSGSSSGTLATLTISGAQVEDEADYYC YSIDTSANLGV FGGGTKLTVL (“LC”) amino acid sequence

Ab 906 1811 QVQLVQSGAEVKKPGASVKVSCQASG YTLTTYDIN WVRQAPGQGLEWMG WMN ADI-41788 Heavy chain variable region

ANSGNTGYAQKFQ GRVTMTRNISISTAYMELSSLGPEDTAVYYC ARGFYKWNDW (“HC”) amino acid sequence

SFDY WGQGTLVTVSS

Ab 906 1812 QSVLTQPPSVSVAPGQTARITC GGNNIGSKSVH WYQQKPGQAPVLVVY DDSDRPS ADI-41788 Light chain variable region

GIPERFSGSNSGNTAPLTISRVEAGDEADYYC QVWDGDSAHHAV FGGGTQLTVL (“LC”) amino acid sequence

Ab 907 1813 QVQLVQSGAEVKKPGSSVKVSCKASG GTFSNYGIS WVRQAPGQGLERLG GIIPIYG ADI-41790 Heavy chain variable region

TANHAQNFQG RVTITADESTSTAYMELSSLRSEDTAVYYC ARDGTFVRYYGMDV W (“HC”) amino acid sequence

GQGTTVTVSS

Ab 907 1814 EIVLTQSPATLFLSPGERATLSC RASQSVSNYLA WFQQKPGQAPRLLIY DTSIRAT GIP ADI-41790 Light chain variable region

ARFSGSGSGTDFTLTISSLEPEDFAFYYC QQRSNWPPT FGGGTKLEIK (“LC”) amino acid sequence

Ab 908 1815 QVQLVQSGGGLVKHGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWAS SISSSS ADI-41792 Heavy chain variable region

SYIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARTEYSSSSPIFDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 908 1816 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLTY GNSNR ADI-41792 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV FGGGTKVTVL (“LC”) amino acid sequence

Ab 909 1817 EVQLQQWGAGLLKPSETLSLTCAVYG GSFSGYYWS WIRQPPGKGLEWIG EINHSG ADI-41794 Heavy chain variable region

STNYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARGTRTIVYCDGDCYQP (“HC”) amino acid sequence

WAYHYYGMDV WGQGTTVTVSS

Ab 909 1818 QSVVTQEPSVSAAPGQKVTISC SGGSSNIGNNYVS WYQHLPGTAPKLLIY DNDKRP ADI-41794 Light chain variable region

S GIPDRFSGSKSGTSATLGITGLQTGDEADYYC GTWDSSLSAVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 910 1819 QVQLVQSGAEVKKPGSSVKVSCQASG GTFSTHALS WVRQTPGHGLEWVG GVLPV ADI-41799 Heavy chain variable region

FGATKYPRKFQG RVTITADKSTNTAYMELSSLRSDDTAVYYC ARVVVHSTITTAKDF (“HC”) amino acid sequence

FSGVHDI WGQGTMVTVSS

Ab 910 1820 DIRMTQSPSTLSASVGDRVTITC RASQTVSSWLA WYQQKPGKAPKLLIY QASSLES G ADI-41799 Light chain variable region

VPSRFSGSGSGTEFTLTISGLQPDDFATYFC QHYNSYSPVT FGGGTKVEIK (“LC”) amino acid sequence

Ab 911 1821 QVQLVQSGAEVKKPGASVKVSCKASG YTFTDYYMH WVRQAPGQGLEWLA WINP ADI-41800 Heavy chain variable region

YTGGTNYAQKFQG RVTLTRDTSVSTTYMEVTRLRSDDTAVYYC ARGESFHH WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 911 1822 QSALTQPASVSGSPGQSITISC TGTSSDIGGYDYVS WYQQHPGKVPKLMIY EVSTRP ADI-41800 Light chain variable region

S GVSIRFSGSKSGNTASLTISGLQAEDEADYYC SSYTRSTITSVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 912 1823 RCTLQQWGAGRVKPSETLSLTCAVYR GPFSGYYWS WIRQPPGKGLEWIG EINLGE ADI-41803 Heavy chain variable region

TNPGGSTHYNPSLRS RLSMSIDTSKKQFSLRVNSVTAADTAVYYC TRGPVSRIYDTS (“HC”) amino acid sequence

GSYSLNYYGMDV WGQGTTVTVSS

Ab 912 1824 DIRMTQSPSSLSASVGDRVTITC RASQGIRNDLG WYQQKPGRAPERLIY PASSLQG ADI-41803 Light chain variable region

GVPSRFIASGSGTEFTLTISNLQPEDFATYYC LQHNSYPRT FGQGTKVEIK (“LC”) amino acid sequence

Ab 913 1825 QVQLQQWGAGLLKPSETLSLTCSVLG GSFSGYYWT WIRQPPGKGLEWIG EITHDG ADI-41804 Heavy chain variable region

SSNYNPSLNS RVTISVDTSNYQFSLKMRSVTAADTAVYYC ARSPDLTIFGGLYFYYGI (“HC”) amino acid sequence

SV WGQGTTVTVSS

Ab 913 1826 DIQMTQSPSSLSASMGDRVTITC RASQDISNYLA WYQQKPGKVPNLLIY AASTLQG ADI-41804 Light chain variable region

GVPSRFSGSGSGTDFTLTISSLQPEDVAIYYC QKYKSAPRT FGQGTKVEIK (“LC”) amino acid sequence

Ab 914 1827 QVQLVQSGAEVKKPGESLKISCKASG YSFTSYWIA WVRQMPGKGLEWMG IIFPGD ADI-41805 Heavy chain variable region

SDTRYSPSFQG QVTISADKSISTAYLQWSSLEASDTAMYYC AKSTTYYYYGLDV WG (“HC”) amino acid sequence

QGTTVTVSS

Ab 914 1828 QPVLTQPASVSGSPGQSITISC TGTSSDVGGYDYVS WYQQYPGKAPKLMIY EVSNR ADI-41805 Light chain variable region

PL GVSNRFSGSRSGYTASLTISGLQAEDETNYYC SSYTSSRTWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 915 1829 EVQLLESGPALVKPTQTLTLTCTFSG FSLTTTRMSVS WIRQPPGKALEWLA RIDWD ADI-41807 Heavy chain variable region

DDKYYSTSLKT RLTISKDTSKNQVVLTMTNMDPVDTATYFC ARVNVYAANGYYSYY (“HC”) amino acid sequence

LDY WGQGTLVTVSS

Ab 915 1830 DIVMTQTPSSLSASVGDRVTITC RTSQSSSRYLN WYQKEPGKAPRLLIY LASALRS GV ADI-41807 Light chain variable region

PSRFSGSGSGTDFTLTISSLQSEDFATYYC QQTYSIPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 916 1831 QVQLVQSGAELKKPGSSVRISCKVSG VTSDNYAIT WVRQAPGQGLEWMG RVIPIF ADI-41808 Heavy chain variable region

PVPQYAQKFQG RVTLSADKSTRTAYLELHSLRSEDTATYYC ATHRPSDS WGQGTLV (“HC”) amino acid sequence

TVSS

Ab 916 1832 DIRVTQSPSTLSASVGDRVTITC RASQNINSWLA WYQQKPGKAPKLLIF KASSLES G ADI-41808 Light chain variable region

VPARFSGSGFGTEFTLTITSLQPDDFASYYC QQYDTYPYP FGQGTKVEIK (“LC”) amino acid sequence

Ab 917 1833 QVTLKESGGGLVQPGGSLRLSCAASG FTFSNYAMS WVRQAPGKGLEWVS AISHSD ADI-41809 Heavy chain variable region

SRTFYADSVKG RFTISRDNSKNTLFLQMDSLRAHDTAVYYC ANVDPSSVTYYGYYYG (“HC”) amino acid sequence

MDV WGQGTTVTVSS

Ab 917 1834 QSVLTQPPSASGTPGQRVTISC SGSSSNIGKNFVY WYQQFPGTAPKRLIY RNNQRP ADI-41809 Light chain variable region

S GVPDRFSGSRSGTSASLAISGLRSEDEADYYC ATWDDSLSGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 918 1835 QVQLVQSGGGVVQPGRSLRLSCAASG FNFHNYAMH WVRQAPGKGLEWVA VISY ADI-41810 Heavy chain variable region

DGGNKHYADSVKG RFTISRDNSKNTLYLQMNSLRPDDTAVYYC ARGHSDWRGDY (“HC”) amino acid sequence

FDF WGQGTLVTVSS

Ab 918 1836 DIQLTQSPATLSVSPGERAILSC RASQNVGTNLA WYQQKPGQAPRLLIY DASTRAT G ADI-41810 Light chain variable region

IPARFSGSGAGTDFTLTISGLQSEDFAVYYC QQYINWPPYT FGQGTKLEIK (“LC”) amino acid sequence

Ab 919 1837 QVQLQQSGPRLVKPSHTLSLTCVIS GDSVSSGSAAWS WIRQSPSRGLEWLG RTYYR ADI-41811 Heavy chain variable region

SKWYYDYAVSVKG RIIQPDTSKNQFSLQLNSVSPEDTAVYYC ARDPDSGNYFHYYG (“HC”) amino acid sequence

MDV WGQGTTVTVSS

Ab 919 1838 DIVMTQSPATLSLSPGERATLSC RASQSVDVYFA WYQQKPGQAPRLLIY DASKRAS ADI-41811 Light chain variable region

GVPARFSGSASGTDFTLTISSLEPEDFAVYYC QQRAKWPPYT FGQGTKLEIK (“LC”) amino acid sequence

Ab 920 1839 EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISAGSS ADI-41812 Heavy chain variable region

YTDYAESVKG RFTISRDNAKNSLYLKMNSLRAEDTAVYYC ARDPGYCSSNSCTVAM (“HC”) amino acid sequence

DV WGQGTTVTVSS

Ab 920 1840 SYELTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNNNR ADI-41812 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDRTLVI FGGGTKLTVL (“LC”) amino acid sequence

Ab 921 1841 EVQLLESGPTLVKPTQTLTLTCTFSG FSLSTFGVGVG WIRQPPGKALECLA LIYWDD ADI-41814 Heavy chain variable region

DKRYSPSLKS RLTITRDTSKNQVVLTMTNMDPVDTATYYC AHRRSSTVTTGFFDY W (“HC”) amino acid sequence

GRGTLVTVSS

Ab 921 1842 QPVLTQPPSVSGAPGQRVTVSC TGNSSNIGAGHGAH WYQQLPGTAPKLLIY GSTD ADI-41814 Light chain variable region

RPS GVPDRFFGSQSGTSASLVITELRAEDEADYYC QSFDSSLSIWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 922 1843 EVQLLESGGGLVKPGGSLRLSCGASG FTFSTSSFN WVRQAPGKGLEWVS SISSTSSY ADI-41815 Heavy chain variable region

VFYADSVKG RFTVSRDNAQNSLYLQMNSLRAEDTAVYYC ARARGVGATIGFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 922 1844 DIVMTQSPLSLPVTPGEPASISC RSSQSLLHSNGYNYLD WYLQKPGQSPQLLIY LGSN ADI-41815 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 923 1845 QVQLVQSGAEVKKPGASVKVSCEASG YTFTDSYIH WVRQAPGQGLEWMG WINP ADI-41816 Heavy chain variable region

NSGGTNYAQKFQG RVTMTRDTSTSTAFIELSRLRSDDTAVYYS ARGVRQQWLVNT (“HC”) amino acid sequence

GDPDYYFDF WGQGTLVTVSS

Ab 923 1846 SYVLTQPPSVSVSPGQTASITC SGDKLGDKYSC WYQQKPGQSPVLVIY QDYKRPS GI ADI-41816 Light chain variable region

PERFSGSNSGNTATLTISGTQAMDEADYYC QAWDRNAGV FGTGTKLTVL (“LC”) amino acid sequence

Ab 924 1847 QVQLVQSGAEVKKPGESLKISCKGPG YSFTTYWIG WVRQMPGKGLEWMG IIYPG ADI-41817 Heavy chain variable region

DSDTKYSPSFQG QVTITADKSIATAYLQWSRLKASDTAVYYC ATVVTYADNIRWFDS (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 924 1848 QSALTQPASVSGSPGQSITISC TGTSGDVGGYKFVS WYQHHPGKAPKLVIY DVANR ADI-41817 Light chain variable region

PS GVSDRFSGSKSGTTASLTISGLQAEDEADYYC SSYTSSSTYV FGTGTKVTAL (“LC”) amino acid sequence

Ab 925 1849 EVQLVESGGGLVQPGGSLRLSCAASG FTVNTNYMS WVRQAPGKGLEWVS IIYSSG ADI-41818 Heavy chain variable region

STSYADSVKG RFTISRDNSENTLYLQMHTLRAEDTAVYYC VRERTPFYYVSSGYWDS (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 925 1850 EIVLTQSPGTLSLSPGERATLSC RASQSVDSSYLA WYQQKPGQAPRLLIF GASSRAT G ADI-41818 Light chain variable region

IPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGFSYT FGQGTKVEIK (“LC”) amino acid sequence

Ab 926 1851 EVQLVESGGGVVQPGRSLRLSCAVSG FTFSTYGMH WVRQTPGRGLEWVA VISYD ADI-41820 Heavy chain variable region

GNHKYYADSVMG RFTISRDNSKDTLYLQVNSLRPEDSAVYYC AKDRIHCPNGVCYV (“HC”) amino acid sequence

HSSFYGLDV WGQGTTVTVSS

Ab 926 1852 QTVVTQEPSLIVSPGGIVTLIC GSSTGAVTSGHYPY WLQQKPGQAPRTLIY DTTNK ADI-41820 Light chain variable region

DS WTPARFSGSLLGGKAALTLSGAQPEDEAQYYC LLSENGPYWV FGGGTKVTVL (“LC”) amino acid sequence

Ab 927 1853 EVQLSESAGGVVQPGGSLRLTCAASG FSFSTNGMH WVRQAPGKGLEWVA FIRYD ADI-41827 Heavy chain variable region

GSKKYYAESVKG RFTISREDSNNTLYLQMNSLRPEDTAVYYC AKEDCSGGTCYHERN (“HC”) amino acid sequence

YYYYGMDV WGQGTTVTVSS

Ab 927 1854 QPVLTQPPSLPVSPGQTASITC SGDKLEYKYAC WYQHKPGQSPVLVIY QDNKRPS GI ADI-41827 Light chain variable region

PERFSGSNSGNTATLTISGTQPMDEADYYCQ AWDSSTVV FGGGTKVTVL (“LC”) amino acid sequence

Ab 928 1855 EVQLVESGGGLVQPGGSLRLSCADSD FTFSTYSMN WVRQAPGKGLEWIS YITGRSS ADI-41828 Heavy chain variable region

AIYYADSVKG RFTISRDNAKNSLFLQMNSLRAEDTAVYYC TTFMAGYSFGHGDAFD (“HC”) amino acid sequence

I WGQGTTVTVSS

Ab 928 1856 SYELTQPPSVSVAPGQTARITC GGNNIGSKSVH WYQQKPGQAPVLVVY DDSDRPS ADI-41828 Light chain variable region

GIPERFSGSNSGNTATLTISRVEAGDEADYYC QVWNSNSDHPHWV FGGGTQLTVL (“LC”) amino acid sequence

Ab 929 1857 EVQLVESGGGLVKPGGSLRLSCAASG FTSSGYNMN WVRQAPGKGLEWVS SISGSS ADI-41829 Heavy chain variable region

SYIHYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ATVGALPGHFDN WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 929 1858 QAVVTQEPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY DNTNR ADI-41829 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSRLTYV FGTGTKVTVL (“LC”) amino acid sequence

Ab 930 1859 QVQLVQSGPAVKKPGASVKVSCKASG YIFTSYGVS WVRQAPGQGLEWMG WISGY ADI-41830 Heavy chain variable region

NGNTDYAQKFQG RVTLTVDSSTGTVYMDLRSLRSDDTAIYYC ARAPPLPGQVYDG (“HC”) amino acid sequence

AGSYLLHGY WGQGTLVTVSS

Ab 930 1860 DIVMTQSPLSLPVTPGEPASISC RSSQSLLHSNGYNYLD WYLQKPGQSPQLLIY LGSN ADI-41830 Light chain variable region

RAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPRT FGQGTKVEIK (“LC”) amino acid sequence

Ab 931 1861 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYAMH WVRQPPGKGLEWVS SISASSS ADI-41831 Heavy chain variable region

FINYADSVKG RFTISRDGARNSLYLQMNSLRAEDTAVYYC VREDYDSSGYGLHWFD (“HC”) amino acid sequence

P WGQGTTVTVSS

Ab 931 1862 SYVLTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQFPGTAPKLLMY GNTN ADI-41831 Light chain variable region

RPS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDRSLSGWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 932 1863 EVQLVESGGGLVQPGGSLRLSCAASG FTFSKYAMN WVRQAPGKGLEWVS SISDSG ADI-41832 Heavy chain variable region

DSRYYADSVKG RFTISRDSSKNTLNLQMNSLRAEDTAVYYC AKAGWELFSPQGAFD (“HC”) amino acid sequence

L WGQGTMVTVSS

Ab 932 1864 EIVMTQSPGTLSLSPGERATLSC RASQSVSSSHLA WYQQKPGQAPRLLIY GASSRDS ADI-41832 Light chain variable region

GIPDRFSGSGSGTDFTLSISRLEPEDFAVYYC QHYGNSPYT FGQGTKVDIK (“LC”) amino acid sequence

Ab 933 1865 EVQLLESGGGLVQPGGSLRLSCAASR FTFSTYAMS WVRQAPGKGLEWVS SISGSG ADI-41833 Heavy chain variable region

DKTFYTDSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARESYYELWTGTYPG (“HC”) amino acid sequence

WELDY WGQGTLVTVSS

Ab 933 1866 DIQLTQSPSSLSASVGDRVTITC RASQDISNYLA WYQQKPGKPPKLLIY AASILES GAP ADI-41833 Light chain variable region

SRFSGSGSGTDFTLTISSLQPEDVGTYYC QKSNSAPRP FGQGTKVEIK (“LC”) amino acid sequence

Ab 934 1867 EVQLLESGGRLVQPGRSLRLSCAASG FTVSGSYMS WVRQAPGKGLEWVS VIYIDG ADI-41834 Heavy chain variable region

GTKYADSVKG RFTISRDNSKNTVYLQMNSLRAEDTAVYYC ARDSSLWYRGGDY WG (“HC”) amino acid sequence

QGTLVTVSS

Ab 934 1868 DIQMTQSPSSLSASVGDRVTITC QANHDISNYLN WYQQKPGKAPKLLIY DASILEA G ADI-41834 Light chain variable region

VPSRFSGSGSGTHFTFTISSLQPEDIATYYC QQFDFRALT FGGGTKVEIK (“LC”) amino acid sequence

Ab 935 1869 EVQLLESGGGLVQPGGSLRLSCAASG FTFSSYAMN WVRQAPGKGLEWVS IISDSG ADI-41835 Heavy chain variable region

GSTYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKATPLKWELLIGSTP (“HC”) amino acid sequence

GYYFDY WGQGTTVTVSS

Ab 935 1870 SYELTQLPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVVIMY QDNKRPS ADI-41835 Light chain variable region

GIPERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTGV FGGGTKVTVL (“LC”) amino acid sequence

Ab 936 1871 EVQLLESGAEVKKPGASVKVSCRASG YTFTSNTLH WVRQAPGQGLEWMG WINAD ADI-41836 Heavy chain variable region

NGNTRYSQKFQG RVTITRDTSANTAYMELSSLISEDTAVYYC AREWSGFWSGLNW (“HC”) amino acid sequence

FEP WGQGTLVTVSS

Ab 936 1872 QSVLTQPPSVSGAPGQRVTISC TGSSSNIGSGNDVH WYQQFPGTAPKVLIY VNSIRP ADI-41836 Light chain variable region

S GVSDRFSGSKSGTSASLAITGLRAEDEADYYC QSYDSSLNGVA FGGGTKLTVL (“LC”) amino acid sequence

Ab 937 1873 QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYGIS WVRQAPGQGLEWMG WISAY ADI-41837 Heavy chain variable region

SGDTDYAQKLQG RVTMTTDTATSTAYMELRSLRSDDTAVYYC ARDAHCSSTNCYID (“HC”) amino acid sequence

LGGAPVDY WGQGTLVTVSS

Ab 937 1874 DIVLTQTPLSLSVTLGQPASISC RSSQSLVYIDGYTYLN WFQQRPGQSPRRLIY KVSN ADI-41837 Light chain variable region

RDS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQGAHWPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 938 1875 EVQLLESGGGVVQPGRSLRLSCAASE FTFRSYAMH WVRQAPGMGLEWVA VTPYD ADI-41838 Heavy chain variable region

GISKYYADSVKG RFTISRDNSKNTLYLQMNSLRPEDTAVYYC ARGFPEPITSWPGYF (“HC”) amino acid sequence

YAMDV WGQGTTVTVSS

Ab 938 1876 QSALTQPASVSGSPGQSITISC TGTTSDVGVYNYVS WYQQHPGKAPKLMIY DVSNR ADI-41838 Light chain variable region

PS GVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTNSDTPVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 939 1877 EVQLLESGGGVVQPGGSLRLSCVASG FTFSAYGMH WVRQAPGKGPEWVA MTRS ADI-41839 Heavy chain variable region

DGNKIYYADSVKG RFTISRDDSKNTLYLEMNSLRPDDTAVYFC AKEVGYGGNSLHY (“HC”) amino acid sequence

WGQGTLVTVSS

Ab 939 1878 SYELIQPPSVSVAPGQTAKITC GGNNIGSKSVH WYQQKPGQAPVLVVF DDSDRPS G ADI-41839 Light chain variable region

IPERFSGSNSGNTATLTISRVEAGDEADYYC QVWDFSSDLWV FGGGTKLTVL (“LC”) amino acid sequence

Ab 940 1879 QVQLVQSGAEVKKPGSSVKVSCKASG DTFSGYAIY WVRQAPGRGLELMG GIIPILG ADI-41840 Heavy chain variable region

TSSYAQRFLG RTSFTADESTSTAYMDLSSLTSADTAMYYC ARKRVTVPVPFDS WGQ (“HC”) amino acid sequence

GTLVTVSS

Ab 940 1880 EIVMTQSPATLSVSPGERATLSC RASQSVSSNLA WYQQKLGQAPRLLIY GASTRAT D ADI-41840 Light chain variable region

IPARFSGSGSGTEFTLTISSLQSEDFVVYYC QQYNNWPWT FGQGTKVEIK (“LC”) amino acid sequence

Ab 941 1881 EVQLLESGGGLVKPGGSLRLSCAASG FSFSYYSMN WVRQTPGKGLEWVS SISDRSS ADI-41841 Heavy chain variable region

YISYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDQYESYAFDI WGQG (“HC”) amino acid sequence

TTVTVSS

Ab 941 1882 DIQVTQSPSSLSASVGDRITITC QASQDVGNYLN WYQQKVGKAPKLLIH DASDLET ADI-41841 Light chain variable region

GVPSRFSGSGSGTYFTFTISSLQPEDFATYYC QPYDNLRPVT FGQGTRLEIK (“LC”) amino acid sequence

Ab 942 1883 QVQLVQSGAEVKKPGASVRVSCKASG YTFTHYDIN WVRQAPGQGLEWMG WINP ADI-41842 Heavy chain variable region

NSGDTDYAQKFQG RVTMTVDTSISTAYLDLRSLTSADAAVYYC ARGGAYAINGYYII (“HC”) amino acid sequence

WFDP WGQGTLVTVSS

Ab 942 1884 DIVVTQSPSSLSASVGDRVTITC RASQSISRYLN WFQKKPGKAPHLLIY AASILQS EVP ADI-41842 Light chain variable region

SRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYNSPYT FGPGTKVDIK (“LC”) amino acid sequence

Ab 943 1885 QVQLQQWGAGLLKPSETLSLTCAVYG GSFSGYYWS WIRQPPGKGLEWIG EINHSG ADI-43638 Heavy chain variable region

STNYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYC ARGVPVLRYFDWLRFGY (“HC”) amino acid sequence

GMDV WGQGTTVTVSS

Ab 943 1886 EIVMTQSPDSLAVSLGERATINC KSSQSVLYSSNNKNYLA WYQQKPGQPPKLLIY W ADI-43638 Light chain variable region

ASTRES GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC QQYYSTPPLT FGGGTKLEIK (“LC”) amino acid sequence

Ab 944 1887 QVQLVQSGSELKKPGASVKVSCKASG YTFTSYAMN WVRQAPGQGLEWMG WINT ADI-43639 Heavy chain variable region

NTGNPTYAQGFTG RFVFSLDTSVSTAYLQISSLKAEDTAVYYC AAYGIHDAFDI WGQ (“HC”) amino acid sequence

GTMVTVSS

Ab 944 1888 DIRLTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIY AASSLQS GVP ADI-43639 Light chain variable region

SRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPRT FGQGTKVEIK (“LC”) amino acid sequence

Ab 945 1889 QVQLVQSGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSS ADI-43640 Heavy chain variable region

SYIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC AREGRDGYNYNFDY W (“HC”) amino acid sequence

GQGTLVTVSS

Ab 945 1890 QSVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-43640 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGVV FGGGTKLTVL (“LC”) amino acid sequence

Ab 946 1891 EVQLVESGGGLVKPGGSLRLSCAASG FTFSDYYMS WIRQAPGKGLEWVS YISSSSSY ADI-43641 Heavy chain variable region

TNYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDFSGQWLVLGYGM (“HC”) amino acid sequence

DV WGQGTTVTVSS

Ab 946 1892 QSVVTQPPSVSGAPGQRVTISCT GSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-43641 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGPV FGGGTKLTVL (“LC”) amino acid sequence

Ab 947 1893 EVQLLESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSS ADI-43642 Heavy chain variable region

YIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYC ARDGADSSYYYYMDV W (“HC”) amino acid sequence

GKGTTVTVSS

Ab 947 1894 QAVVTQPPSVSGAPGQRVTISC TGSSSNIGAGYDVH WYQQLPGTAPKLLIY GNSNR ADI-43642 Light chain variable region

PS GVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSV FGGGTKLTVL (“LC”) amino acid sequence

EXEMPLARY EMBODIMENTS

1. An isolated antibody or antigen-binding fragment thereof that cross-competes for binding or specifically binds to the same epitope(s) of a Respiratory Syncytial Virus (RSV) fusion glycoprotein (F) (“an anti-RSV F antibody”) as an antibody or antigen-binding fragment thereof comprising a CDRH3 amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a CDRH3 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 465 as disclosed in Table 5.

2. An isolated antibody or antigen-binding fragment thereof that cross-competes for binding or specifically binds to the same epitope(s) of a Respiratory Syncytial Virus (RSV) fusion glycoprotein (F) (“an anti-RSV F antibody”) as an antibody or antigen-binding fragment thereof comprising a CDRH2 amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a CDRH2 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

3. An isolated antibody or antigen-binding fragment thereof that cross-competes for binding or specifically binds to the same epitope(s) of a Respiratory Syncytial Virus (RSV) fusion glycoprotein (F) (“an anti-RSV F antibody”) as an antibody or antigen-binding fragment thereof comprising a CDRH1 amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a CDRH1 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

4. An isolated antibody or antigen-binding fragment thereof that cross-competes for binding or specifically binds to the same epitope(s) of a Respiratory Syncytial Virus (RSV) fusion glycoprotein (F) (“an anti-RSV F antibody”) as an antibody or antigen-binding fragment thereof comprising a CDRL3 amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a CDRL3 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

5. An isolated antibody or antigen-binding fragment thereof that cross-competes for binding or specifically binds to the same epitope(s) of a Respiratory Syncytial Virus (RSV) fusion glycoprotein (F) (“an anti-RSV F antibody”) as an antibody or antigen-binding fragment thereof comprising a CDRL2 amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a CDRL2 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

6. An isolated antibody or antigen-binding fragment thereof that cross-competes for binding or specifically binds to the same epitope(s) of a Respiratory Syncytial Virus (RSV) fusion glycoprotein (F) (“an anti-RSV F antibody”) as an antibody or antigen-binding fragment thereof comprising a CDRL1 amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a CDRL1 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

7. The isolated anti-RSV F antibody of any one of embodiments 1 to 6, comprising (i) the CDRH3 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5; (ii) the CDRH2 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5; (iii) the CDRH1 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5; (iv) the CDRL3 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5; (v) the CDRL2 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5; (vi) the CDRL1 amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5; or (vii) any combination of two or more of (i), (ii), (iii), (iv), (v), and (vi).

8. An isolated antibody or antigen-binding fragment thereof that cross-competes for binding or specifically binds to the same epitope(s) of a Respiratory Syncytial Virus (RSV) fusion glycoprotein (F) (“an anti-RSV F antibody”) as an antibody or antigen-binding fragment thereof comprising (i) a heavy chain variable region (V H ) that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a V H amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5, and/or (ii) a light chain variable region (V L ) that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a V L amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

9. The isolated anti-RSV F antibody of embodiment 8, comprising (i) the V H amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5; and/or (ii) the V L amino acid sequence of an antibody selected from Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

10. The isolated anti-RSV F antibody of any one of embodiments 1 to 9, which is selected from the group consisting of Antibody Number 1 through Antibody Number 947 as disclosed in Table 5.

11. The isolated anti-RSV F antibody of any one of embodiments 1 to 10, which binds to an epitope comprising site Ø, site I, site II, site III, site IV, or site V of RSVF.

12. The isolated anti-RSV F antibody of any one of embodiments 1 to 11, which binds to an epitope on prefusion F (preF), preferably antigenic site III.

13. The isolated anti-RSV F antibody of any one of embodiments 1 to 12, which binds to prefusion F (preF) with high affinity but does not bind to or binds with low affinity to postfusion F (postF).

14. The isolated anti-RSV F antibody of any one of embodiments 1 to 12, which binds to an epitope on postfusion F (post F), preferably antigenic site I.

15. The isolated anti-RSV F antibody of any one of embodiments 1 to 14, which does not compete with D25 for binding to RSV F.

16. The isolated anti-RSV F antibody of any one of embodiments 1 to 15, which competes with MPE8 and/or motavizumab for binding to RSV F.

17. The isolated anti-RSV F antibody of any one of embodiments 1 to 16, which is a neutralizing antibody.

18. The isolated anti-RSV F antibody of embodiment 17, which has a neutralizing activity (IC 50 ) of less than 100 μg/ml, 50 μs/ml, 25 μs/ml, 10 μg/ml, 5 μg/ml, 1 μg/ml, 0.5 μg/ml, 0.1 μg/ml, or 0.05 μg/ml.

19. The isolated anti-RSV F antibody of any one of embodiments 1 to 18, which binds to RSV prefusion F with a K D value of less than 50 nM, 25 nM, 10 nM, 5 nM, 1 nM, 0.5 nM, or

0.1 nM as measured by surface plasmon resonance.

20. The isolated anti-RSV F antibody of any one of embodiments 1 to 19, which binds to RSV prefusion F through one or both of the following interactions:

• a) Tyr33 in CDRL1 and Tyr93 in CDRL3 both contact the α6-α7 loop of RSV prefusion F; and • b) five consecutive serine residues, preferably followed by a tyrosine residue (Tyr56), in CDRH2 form a network of hydrogen bonds with Asp310 on (36 of RSV prefusion F.

21. The isolated anti-RSV F antibody of any one of embodiments 1 to 20, which has a clean or low polyreactivity profile.

22. The isolated anti-RSV F antibody of any one of embodiments 1 to 21, which is a full-length IgG1 monoclonal antibody.

23. The isolated anti-RSV F antibody of any one of embodiments 1 to 22, which comprises a Fc region that has been modified to alter effector function, half-life, proteolysis, and/or glycosylation.

24. The isolated anti-RSV F antibody of any one of embodiments 1 to 23, which is derivatized.

25. An isolated nucleic acid sequence or nucleic acid sequences encoding an antibody or antigen-binding fragment thereof according to any one of embodiments 1 to 24.

26. An expression vector or vectors comprising the isolated nucleic acid sequence according to embodiment 25.

27. A host cell comprising the isolated nucleic acid sequence(s) according to embodiment 25 or the expression vector(s) according to embodiment 26.

28. The host cell of embodiment 27, which is a mammalian cell, a bacterial cell, a fungal cell, a yeast cell, or an insect cell.

29. A method for producing an isolated antibody or antigen-binding fragment thereof that specifically binds to Respiratory Syncytial Virus (RSV) fusion glycoprotein (F) (“an anti-RSV F antibody”) comprising expressing the nucleic acid sequence(s) of embodiment 25 or culturing the host cell of embodiment 27 or 28 under conditions that provide for expression of the anti-RSV F antibody and optionally recovering the anti-RSV F antibody from the host cell and/or culture medium.

30. The method of embodiment 29, wherein the host cell is a yeast cell or a mammalian cell.

31. A pharmaceutical composition comprising (i) the anti-RSV F antibody of any one of embodiments 1 to 24, the nucleic acid sequence(s) of embodiment 25, the expression vector(s) of embodiment 26, or the host cell of embodiments 27 or 28; and (ii) a pharmaceutically acceptable carrier and/or excipient.

32. The pharmaceutical composition of embodiment 31 for use in preventing or treating a RSV infection in a subject.

33. The pharmaceutical composition of embodiment 32, wherein the subject is a human, preferably an infant.

34. A method of preventing or treating a Respiratory Syncytial Virus (RSV) infection in a subject, comprising administering to the subject in need thereof an effective amount of the anti-RSV F antibody of any one of embodiments 1 to 24, the isolated nucleic acid sequence(s) of embodiment 25, the expression vector(s) of embodiment 26, or the host cell(s) of embodiment 27 or 28, optionally in association with a further prophylactic and/or therapeutic agent.

35. The method of embodiment 34, wherein the further prophylactic and/or therapeutic agent is selected from an antiviral agent; a vaccine specific for RSV; a vaccine specific for influenza virus; a vaccine specific for metapneumovirus (MPV); an siRNA specific for a RSV antigen; an siRNA specific for a MPV antigen; a second anti-RSV antibody; an anti-MPV antibody; an anti-IL4R antibody; an anti-influenza antibody; and a NSAID.

36. The method of embodiment 34 or 35, wherein the subject is human, preferably an infant.

37. A method of preventing or treating a Respiratory Syncytial Virus (RSV) infection in a human subject, comprising administering to the subject in need thereof an effective amount of the pharmaceutical composition of any one of embodiments 31 to 33.

38. The method of embodiment 37, wherein the human subject is an infant.

39. A method for detecting a Respiratory Syncytial Virus (RSV) infection in a subject, comprising obtaining a sample from the subject; contacting the sample with the anti-RSV F antibody of any one of embodiments 1 to 24; and detecting the presence of a complex between the anti-RSV F antibody and the RSV fusion glycoprotein (F), wherein detection of the complex indicates the presence of RSV.

40. The method of embodiment 39, wherein the subject is a human, preferably an infant.

41. An isolated antibody or antigen-binding polypeptide comprising a VH CDR3 having an amino acid sequence according to an antibody number in Table 9B.

42. An isolated antibody or antigen-binding polypeptide comprising a VH CDR3 having an amino acid sequence according to an ADI listed in Table 8.

43. An isolated antibody or antigen binding polypeptide characterized by ability to neutralize respiratory syncytial virus (RSV).

44. An isolated antibody or antigen binding polypeptide characterized by high affinity binding to RSV F.

45. An isolated antibody or antigen binding polypeptide characterized by high affinity binding to RSV prefusion F (preF).

46. An isolated antibody having an amino acid sequence according to:

(i) Antibody Number 2, 71, 112, 217, 227, 228, 249, 466, 467, 469, 470, 832, 471, 516, 527, 532, 543, 544, 551, 554, 571, 578, 581, 592, 615, 641, 843, 868, or 870;

(ii) an Antibody Number of (i) with no more than 3 amino acid substitutions, additions, or deletions;

(iii) an Antibody Number of (i) with no more than 3, 2, or 1 amino acid substitution(s), addition(s), or deletion(s) in a CDR; or

(iv) an Antibody Number of (i) with no more than 3, 2, or 1 amino acid substitution(s), addition(s), or deletion(s) in CDRH3.

47. An antibody or antigen-binding polypeptide according to any preceding embodiment having an IC 50 of less than 300 pM for neutralization of RSV.

48. An antibody or antigen-binding polypeptide according to any preceding embodiment having an IC 50 of less than 200 pM for neutralization of RSV.

49. An antibody or antigen-binding polypeptide according to any preceding embodiment having an IC 50 of less than 100 pM for neutralization of RSV.

50. An antibody or antigen-binding polypeptide according to any preceding embodiment characterized by binding affinity to pre-F with a kD of less than 10 nM.

51. An antibody or antigen-binding polypeptide according to any preceding embodiment characterized by a binding affinity to pre-F that is at least 10, 100, or 1000 fold greater than binding affinity to post-F.

52. An antibody or antigen-binding polypeptide according to any preceding embodiment characterized by high affinity binding to RSV F site III.

53. A nucleic acid molecule encoding an antibody or antigen binding protein according to any preceding embodiment.

54. A vector comprising a nucleic acid molecule encoding an antibody or antigen binding protein according to any preceding embodiment.

55. A cell comprising a vector according to claim 54 .

Citations

This patent cites (7)

  • US20140141044
  • US20140271653
  • US20150118233
  • US20190075433
  • USWO-0198361
  • USWO-2017/075124
  • USWO-2017/172890